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Artykuły w czasopismach na temat "Transcriptomie"
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Ochsner, Scott A., Christopher M. Watkins, Apollo McOwiti, Xueping Xu, Yolanda F. Darlington, Michael D. Dehart, Austin J. Cooney, David L. Steffen, Lauren B. Becnel i Neil J. McKenna. "Transcriptomine, a web resource for nuclear receptor signaling transcriptomes". Physiological Genomics 44, nr 17 (1.09.2012): 853–63. http://dx.doi.org/10.1152/physiolgenomics.00033.2012.
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The nuclear receptor (NR) superfamily of ligand-regulated transcription factors directs ligand- and tissue-specific transcriptomes in myriad developmental, metabolic, immunological, and reproductive processes. The NR signaling field has generated a wealth of genome-wide expression data points, but due to deficits in their accessibility, annotation, and integration, the full potential of these studies has not yet been realized. We searched public gene expression databases and MEDLINE for global transcriptomic datasets relevant to NRs, their ligands, and coregulators. We carried out extensive, deep reannotation of the datasets using controlled vocabularies for RNA Source and regulating molecule and resolved disparate gene identifiers to official gene symbols to facilitate comparison of fold changes and their significance across multiple datasets. We assembled these data points into a database, Transcriptomine ( http://www.nursa.org/transcriptomine ), that allows for multiple, menu-driven querying strategies of this transcriptomic “superdataset,” including single and multiple genes, Gene Ontology terms, disease terms, and uploaded custom gene lists. Experimental variables such as regulating molecule, RNA Source, as well as fold-change and P value cutoff values can be modified, and full data records can be either browsed or downloaded for downstream analysis. We demonstrate the utility of Transcriptomine as a hypothesis generation and validation tool using in silico and experimental use cases. Our resource empowers users to instantly and routinely mine the collective biology of millions of previously disparate transcriptomic data points. By incorporating future transcriptome-wide datasets in the NR signaling field, we anticipate Transcriptomine developing into a powerful resource for the NR- and other signal transduction research communities.
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Ali, Abdullah Mahmood, i Azra Raza. "scRNAseq and High-Throughput Spatial Analysis of Tumor and Normal Microenvironment in Solid Tumors Reveal a Possible Origin of Circulating Tumor Hybrid Cells". Cancers 16, nr 7 (8.04.2024): 1444. http://dx.doi.org/10.3390/cancers16071444.
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Metastatic cancer is a leading cause of death in cancer patients worldwide. While circulating hybrid cells (CHCs) are implicated in metastatic spread, studies documenting their tissue origin remain sparse, with limited candidate approaches using one–two markers. Utilizing high-throughput single-cell and spatial transcriptomics, we identified tumor hybrid cells (THCs) co-expressing epithelial and macrophage markers and expressing a distinct transcriptome. Rarely, normal tissue showed these cells (NHCs), but their transcriptome was easily distinguishable from THCs. THCs with unique transcriptomes were observed in breast and colon cancers, suggesting this to be a generalizable phenomenon across cancer types. This study establishes a framework for HC identification in large datasets, providing compelling evidence for their tissue residence and offering comprehensive transcriptomic characterization. Furthermore, it sheds light on their differential function and identifies pathways that could explain their newly acquired invasive capabilities. THCs should be considered as potential therapeutic targets.
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Chen, Wanze, Orane Guillaume-Gentil, Pernille Yde Rainer, Christoph G. Gäbelein, Wouter Saelens, Vincent Gardeux, Amanda Klaeger i in. "Live-seq enables temporal transcriptomic recording of single cells". Nature 608, nr 7924 (17.08.2022): 733–40. http://dx.doi.org/10.1038/s41586-022-05046-9.
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AbstractSingle-cell transcriptomics (scRNA-seq) has greatly advanced our ability to characterize cellular heterogeneity1. However, scRNA-seq requires lysing cells, which impedes further molecular or functional analyses on the same cells. Here, we established Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy2,3, thus allowing to couple a cell’s ground-state transcriptome to its downstream molecular or phenotypic behaviour. To benchmark Live-seq, we used cell growth, functional responses and whole-cell transcriptome read-outs to demonstrate that Live-seq can accurately stratify diverse cell types and states without inducing major cellular perturbations. As a proof of concept, we show that Live-seq can be used to directly map a cell’s trajectory by sequentially profiling the transcriptomes of individual macrophages before and after lipopolysaccharide (LPS) stimulation, and of adipose stromal cells pre- and post-differentiation. In addition, we demonstrate that Live-seq can function as a transcriptomic recorder by preregistering the transcriptomes of individual macrophages that were subsequently monitored by time-lapse imaging after LPS exposure. This enabled the unsupervised, genome-wide ranking of genes on the basis of their ability to affect macrophage LPS response heterogeneity, revealing basal Nfkbia expression level and cell cycle state as important phenotypic determinants, which we experimentally validated. Thus, Live-seq can address a broad range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.
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Callaway, Edward M., Hong-Wei Dong, Joseph R. Ecker, Michael J. Hawrylycz, Z. Josh Huang, Ed S. Lein, John Ngai i in. "A multimodal cell census and atlas of the mammalian primary motor cortex". Nature 598, nr 7879 (6.10.2021): 86–102. http://dx.doi.org/10.1038/s41586-021-03950-0.
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AbstractHere we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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MA, Hoi Tang, Chun Yin YU i Lau Yan NG. "Abstract 7102: The central dogma of hepatocellular carcinoma: Genomic, transcriptomic, and proteomic changes". Cancer Research 84, nr 6_Supplement (22.03.2024): 7102. http://dx.doi.org/10.1158/1538-7445.am2024-7102.
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Abstract Cancer is a disease condition characterized by remarkable heterogeneity, wherein numerous molecular features display considerable disparities even with the same patient cohorts, leading to varied treatment outcomes. The primary factor contributing to the substantial differences observed across cancers stems from unique combinations of genetic mutations. Epigenetic alterations further contribute to differential gene expression and splicing, thereby enhancing transcriptomic diversity. The protein products originating from the cancer transcriptome constitute the specific intracellular and extracellular environment, consequently exerting supplementary effects on epigenetic, transcriptomic, and proteomic changes. The complex interplay and mutual influence between genetic aberrations, transcriptomes, and proteomes significantly contribute to shaping the extensive spectrum of molecular characteristics observed in cancer. With label-free mass spectrometry, RNA-sequencing, and low-pass whole genome sequencing, the quantification of the proteome, transcriptome, and genetic abbreviation of the cancer can be evaluated. With the mouse hydrodynamic tail vein injection (HDVI) models of hepatocellular carcinoma (HCC), different subtypes of HCC derived from different genetic abbreviations can be generated. With the proteome, transcriptome, and genetic abbreviation data of the better-defined HCC from HDVI models and HCC patients, the patient-derived HCC can be classified according to the origin of the genetic abbreviation used in the generation of the HDVI-derived HCC. Furthermore, the proteome of patient-derived plasma will be analyzed, and the signature change unique to HCC classified by different origins of genetic abbreviation will provide an abstract of the proteome, transcriptome, and genetic abbreviation of the HCC tissue. The transcriptomics and proteomics data of HDVI mice produced from five distinct sets of genetic abbreviations have been measured. The proteome and transcriptome of tissue, as well as the proteome of plasma, from a small cohort of HCC patients were studied and classified using this resource to illuminate the fundamental landscape of HCC. The final results will be presented and discussed at the meeting. Citation Format: Hoi Tang MA, Chun Yin YU, Lau Yan NG. The central dogma of hepatocellular carcinoma: Genomic, transcriptomic, and proteomic changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7102.
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Gorbunova, Vera. "COMPARATIVE TRANSCRIPTOMIC OF LONGEVITY". Innovation in Aging 7, Supplement_1 (1.12.2023): 432. http://dx.doi.org/10.1093/geroni/igad104.1423.
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Abstract Transcriptome analysis provides a nuanced view into the changes that occur in cells and tissues. Transcriptome changes rapidly and reproducibly in response to physiological influences and environmental insults. Recent years have seen an exponential increase in transcriptome data at bulk, single cell and spatial resolution that allows insights into the mechanisms and regulatory pathways of aging and longevity. In this session Drs. Gorbunova (University of Rochester) and Gladyshev (Harvard Medical School) will discuss comparative transcriptomics of longevity across species with diverse lifespans that revealed unique signatures of longevity and the integration of transcriptome and proteome data. Dr. Gladyshev will discuss development of transcriptomic clocks of measuring biological aging. Dr. Artyomov will discuss single-cell resolution approaches to reveal aspects of immune aging in humans, and Dr. Palovics will present the use of transcriptomics to understand rejuvenating effects of heterochronic parabiosis.
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Nesterenko, Maksim, i Aleksei Miroliubov. "From head to rootlet: comparative transcriptomic analysis of a rhizocephalan barnacle Peltogaster reticulata (Crustacea: Rhizocephala)". F1000Research 11 (27.05.2022): 583. http://dx.doi.org/10.12688/f1000research.110492.1.
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Background: Rhizocephalan barnacles stand out in the diverse world of metazoan parasites. The body of a rhizocephalan female is modified beyond revealing any recognizable morphological features, consisting of the interna, the system of rootlets, and the externa, a sac-like reproductive body. Moreover, rhizocephalans have an outstanding ability to control their hosts, literally turning them into “zombies”. Despite all these amazing traits, there is no genomic and transcriptomic data about any Rhizocephala. Methods: We collected transcriptomes from four body parts of an adult female rhizocephalan Peltogaster reticulata: externa and main, growing, and thoracic parts of the interna. We used all prepared data for the de novo assembly of the reference transcriptome. Next, a set of encoded proteins was determined, the expression levels of protein-coding genes in different parts of the parasite body were calculated and lists of enriched bioprocesses were identified. We also in silico identified and analyzed sets of potential excretory / secretory proteins. Finally, we applied phylostratigraphy and evolutionary transcriptomics approaches to our data. Results: The assembled reference transcriptome included transcripts of 12,620 protein-coding genes and was the first for both P. reticulata and Rhizocephala. Based on the results obtained, the spatial heterogeneity of protein-coding genes expression in different regions of P. reticulata adult female body was established. The results of both transcriptomic analysis and histological studies indicated the presence of germ-like cells in the lumen of the interna. The potential molecular basis of the interaction between the nervous system of the host and the parasite's interna was also determined. Given the prolonged expression of development-associated genes, we suggest that rhizocephalans “got stuck in the metamorphosis”, even in their reproductive stage. Conclusions: The results of the first comparative transcriptomic analysis for Rhizocephala not only clarified but also expanded the existing ideas about the biology of this amazing parasites.
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Nesterenko, Maksim, i Aleksei Miroliubov. "From head to rootlet: comparative transcriptomic analysis of a rhizocephalan barnacle Peltogaster reticulata (Crustacea: Rhizocephala)". F1000Research 11 (9.01.2023): 583. http://dx.doi.org/10.12688/f1000research.110492.2.
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Background: Rhizocephalan barnacles stand out in the diverse world of metazoan parasites. The body of a rhizocephalan female is modified beyond revealing any recognizable morphological features, consisting of the interna, a system of rootlets, and the externa, a sac-like reproductive body. Moreover, rhizocephalans have an outstanding ability to control their hosts, literally turning them into “zombies”. Despite all these amazing traits, there are no genomic or transcriptomic data about any Rhizocephala. Methods: We collected transcriptomes from four body parts of an adult female rhizocephalan Peltogaster reticulata: the externa, and the main, growing, and thoracic parts of the interna. We used all prepared data for the de novo assembly of the reference transcriptome. Next, a set of encoded proteins was determined, the expression levels of protein-coding genes in different parts of the parasite’s body were calculated and lists of enriched bioprocesses were identified. We also in silico identified and analyzed sets of potential excretory / secretory proteins. Finally, we applied phylostratigraphy and evolutionary transcriptomics approaches to our data. Results: The assembled reference transcriptome included transcripts of 12,620 protein-coding genes and was the first for any rhizocephalan. Based on the results obtained, the spatial heterogeneity of protein-coding gene expression in different regions of the adult female body of P. reticulata was established. The results of both transcriptomic analysis and histological studies indicated the presence of germ-like cells in the lumen of the interna. The potential molecular basis of the interaction between the nervous system of the host and the parasite's interna was also determined. Given the prolonged expression of development-associated genes, we suggest that rhizocephalans “got stuck in their metamorphosis”, even at the reproductive stage. Conclusions: The results of the first comparative transcriptomic analysis for Rhizocephala not only clarified but also expanded the existing ideas about the biology of these extraordinary parasites.
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Li, Youcheng, Leann Lac, Qian Liu i Pingzhao Hu. "ST-CellSeg: Cell segmentation for imaging-based spatial transcriptomics using multi-scale manifold learning". PLOS Computational Biology 20, nr 6 (27.06.2024): e1012254. http://dx.doi.org/10.1371/journal.pcbi.1012254.
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Spatial transcriptomics has gained popularity over the past decade due to its ability to evaluate transcriptome data while preserving spatial information. Cell segmentation is a crucial step in spatial transcriptomic analysis, as it enables the avoidance of unpredictable tissue disentanglement steps. Although high-quality cell segmentation algorithms can aid in the extraction of valuable data, traditional methods are frequently non-spatial, do not account for spatial information efficiently, and perform poorly when confronted with the problem of spatial transcriptome cell segmentation with varying shapes. In this study, we propose ST-CellSeg, an image-based machine learning method for spatial transcriptomics that uses manifold for cell segmentation and is novel in its consideration of multi-scale information. We first construct a fully connected graph which acts as a spatial transcriptomic manifold. Using multi-scale data, we then determine the low-dimensional spatial probability distribution representation for cell segmentation. Using the adjusted Rand index (ARI), normalized mutual information (NMI), and Silhouette coefficient (SC) as model performance measures, the proposed algorithm significantly outperforms baseline models in selected datasets and is efficient in computational complexity.
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Tao, Feng, Chuanzhu Fan, Yimin Liu, Subashini Sivakumar, Kurt P. Kowalski i Edward M. Golenberg. "Optimization and application of non-native Phragmites australis transcriptome assemblies". PLOS ONE 18, nr 1 (23.01.2023): e0280354. http://dx.doi.org/10.1371/journal.pone.0280354.
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Phragmites australis (common reed) has a cosmopolitan distribution and has been suggested as a model organism for the study of invasive plant species. In North America, the non-native subspecies (ssp. australis) is widely distributed across the contiguous 48 states in the United States and large parts of Canada. Even though millions of dollars are spent annually on Phragmites management, insufficient knowledge of P. australis impeded the efficiency of management. To solve this problem, transcriptomic information generated from multiple types of tissue could be a valuable resource for future studies. Here, we constructed forty-nine P. australis transcriptomes assemblies via different assembly tools and multiple parameter settings. The optimal transcriptome assembly for functional annotation and downstream analyses was selected among these transcriptome assemblies by comprehensive assessments. For a total of 422,589 transcripts assembled in this transcriptome assembly, 319,046 transcripts (75.5%) have at least one functional annotation. Within the transcriptome assembly, we further identified 1,495 transcripts showing tissue-specific expression pattern, 10,828 putative transcription factors, and 72,165 candidates for simple sequence repeats markers. The identification and analyses of predicted transcripts related to herbicide- and salinity-resistant genes were shown as two applications of the transcriptomic information to facilitate further research on P. australis. Transcriptome assembly and selection would be important for the transcriptome annotation. With this optimal transcriptome assembly and all relative information from downstream analyses, we have helped to establish foundations for future studies on the mechanisms underlying the invasiveness of non-native P. australis subspecies.
Rozprawy doktorskie na temat "Transcriptomie"
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Maynaud, Géraldine. "Adaptation aux métaux lourds de populations de rhizobia impliquées dans la phytostabilisation de déblais miniers : Identification des mécanismes d’adaptation au Zn et au Cd, et structuration des populations de rhizobia adaptées aux sites miniers". Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20074/document.
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La symbiose entre Anthyllis vulneraria et Mesorhizobium metallidurans, mise en évidence dans l'ancienne mine Zn/Pb des Avinières à St Laurent-le-Minier (Gard) permet une entrée d'azote dans les sols grâce à la fixation biologique qui favorise l'installation d'une végétation pérenne d'intérêt pour limiter la pollution métallique via l'érosion éolienne et hydrique. M. metallidurans ayant la particularité de résister à de fortes concentrations en Zn et Cd, la recherche des gènes d'adaptation aux métaux lourds a été mise en œuvre pour mieux connaitre cette bactérie impliquée dans des opérations de phytostabilisation, par des approches de génétique moléculaire et de transcriptomie (RNAseq). Les gènes codant pour des systèmes de séquestration, d'exclusion, de réduction et d'efflux des métaux lourds, dont cadA1, codant pour une PIB-ATPase exportant Cd/Zn ont été identifiés chez deux souches métallicoles associées à Anthyllis ; M. metallidurans STM 2683T (mine des Avinières) et Mesorhizobium sp. STM 4661 (mine d'Eylie). Une étude fonctionnelle de cadA1 a permis de caractériser son rôle dans la résistance aux métaux lourds chez M. metallidurans. Ce gène a ensuite été testé comme marqueur de résistance pour étudier la diversité et la répartition des symbiotes d'Anthyllis sur des sites miniers et non pollués. Pour cela ce travail a été complété par des analyses phénotypiques de tolérance au Zn et Cd et des analyses phylogénétiques basées sur des marqueurs taxonomiques et symbiotiques. La contrainte métallique exercée par les environnements miniers semble influencer la composition et la diversité bactérienne avec une plus forte proportion (i) de phénotype métallicole lié à la présence du gène cadA1 et (ii) de rhizobia appartenant à M. metallidurans ou à une espèce très proche. La plante hôte semble quant à elle influencer la diversité symbiotique des rhizobia, indépendamment de la contrainte métalliqueEfficient nitrogen-fixing symbiosis between Anthyllis vulneraria and Mesorhizobium metallidurans, identified in the highly Zn/Pb polluted mining site of Avinières (St Laurent-le-Minier, Gard county, France) has recently been described as a potential key bioremediation agent for stimulating the growth of a sustainable plant cover and thus limit heavy metal dispersion from contaminated sites. M. metallidurans strains were shown to be resistant to high Zn and Cd concentrations. The aim of our work was to identify and characterize genes involved in heavy metal adaptation in M. metallidurans by using genetic and transcriptomic approaches (RNAseq technology). Putative genes involved in heavy metal adaptation mechanisms such as exclusion, binding, reduction and efflux, like cadA1, encoding an efflux system PIB-type ATPase involved in Zn and Cd export, were identified in two Mesorhizobium strains associated with Anthyllis: M. metallidurans STM 2683T (Avinières mine) and Mesorhizobium sp. STM 4661 (Eylie mine). Functional studies allowed us to characterize the cadA1 efflux protein as involved in metal tolerance in M. metallidurans. Then, cadA1 was used as a metal-resistance marker to study the diversity and the distribution of Anthyllis symbionts from mine soils and unpolluted soils. This work was completed by Zn- and Cd-tolerance phenotype assays and phylogenetic analyses using taxonomical and symbiotic markers. Metals in mine environments seemed to influence the bacterial composition and the diversity with a high proportion of (i) metal-tolerant phenotypes consistent with the detection of the cadA1 gene and (ii) strains belonging to the M. metallidurans species or to a bacterial species close to it. The plant-hosts seemed to impact symbiotic diversity independently of the metal-tolerant property
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Dubé, Delphine. "Différence dans la capacité de fibroblastes à être reprogrammés par le cytoplasme de l'ovocyte : étude d'une situation différentielle chez le bovin". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS252.
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La reprogrammation, qui est la réversion d’un noyau d’un état somatique vers un état moins différencié, constitue un enjeu majeur pour la thérapie cellulaire. Cependant, les mécanismes initiaux qui président à la reprogrammation restent mal connus. Le transfert nucléaire (clonage) met à profit les propriétés de reprogrammation uniques du cytoplasme ovocytaire, et constitue une approche expérimentale intéressante pour analyser ces processus. Le but de cette thèse est d’étudier la différence de capacité de cellules fibroblastiques à être reprogrammées efficacement, en tirant partie d’une situation-modèle d'efficacité différentielle de reprogrammation après clonage chez le bovin. Ce modèle est constitué de deux lots de fibroblastes donneurs de noyaux, qui forment des embryons clonés dont la différence d’efficacité de développement à terme varie d’un facteur 8. L’analyse des cellules donneuses a montré une augmentation des anomalies de ploïdie dans les cellules à faible potentiel, et la similitude transcriptomique entre les cellules donneuses, alors que la comparaison des transcriptomes des embryonsclonés a montré des différences de reprogrammation de l’expression génique dès le stade suivant l’activation du génome embryonnaire. Des différences de méthylation de l’ADN entre cellules donneuses ont été observées dans les promoteurs de gènes candidats différentiellement reprogrammés, ainsi que dans une analyse plus globale par RRBS. Nous avons enfin étudié la distribution des cellules filles des deux premiers blastomères au stade blastocyste, la distribution « orthogonale » et l’aptitude au développement à terme des embryons de souris clonés étant liées (Liu et al., 2012). Nous avons montré l’existence de trois distributions dans les embryons fécondés mais n’avons pas observé de différence de proportions de celles-ci entre embryons bovins clonés. En conclusion, dans notre modèle, la distribution des cellules filles des deux premiers blastomères au stade blastocyste ne semble pas associée à l’efficacité de reprogrammation dans les embryons bovins clonés, contrairement aux différences épigénétiques entre cellules donneusesReprogramming, which is the return of a nucleus from a somatic state to a less differentiated state, is a major issue for cell therapy. However, the initial mechanisms governing the reprogramming remain poorly understood. Nuclear transfer (cloning) takes advantage of the unique reprogramming properties of the oocyte cytoplasm, and therefore is an interesting experimental approach to analyze these processes. The aim of this thesis is to study the difference in fibroblasts’ ability to be reprogrammed by taking advantage of a model-situation of differential reprogramming efficiency after cloning in cattle. This model consists of two batches of donor fibroblasts, which form cloned embryos having an 8 fold difference in development to term efficiency. Analysis of donor cells has shown increase ploidy abnormalities in cells of low potential, and transcriptomic similarity between the donor cells, whereas comparison ofcloned embryos transcriptomes showed gene expression reprogramming differences just after embryonic genome activation. Differences in DNA methylation between donor cells were observed in the promoters of candidate genes differentially reprogrammed and in a more comprehensive analysis by RRBS. Finally we studied the distribution of the first two blastomeres’ daughter cells at the blastocyst stage, as an "orthogonal" distribution and development to term of mice cloned embryos are linked (Liu et al., 2012). We have shown the existence of three distributions in the fertilized embryos but haven’t seen any difference of proportions between bovine cloned embryos. In conclusion, in our model, the distribution of the first two blastomeres’ daughter cells at the blastocyst stage does not seem related to the reprogramming efficiency in bovine cloned embryos, unlike epigenetic differences between donor cells
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Laplante, Pierre. "Effect of MisMatch Repair Deficiency on metastasis occurrence modelized in a syngeneic mouse model". Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASL101.
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Contexte : Le cancer colorectal (CCR) déficient en réparation des mésappariements (MMR-D), hypermuté et aux microsatellites instables (MSI) est moins enclin au développement de métastases, et présente un pronostic défavorable après récidive, par rapport au CCR aux microsatellites stables (MSS). Les mécanismes derrière ces deux phénomènes sont encore inexpliqués, principalement en raison du manque d'un bon modèle in vivo de cancer métastatique MSI.Méthodes : Nous avons inactivé le gène Msh2 dans la lignée cellulaire de cancer du sein 4T1luc+, exprimant la luciférase. Le phénotype MMR-D, marqué par une accumulation de mutations ponctuelles à l'échelle du génome et d'insertion-délétion (indels) aux sites de microsatellites, a été établi par des passages sériels in vitro avant l'injection orthotopique dans le coussinet adipeux mammaire inférieur gauche de souris BALB/c. Le développement métastatique a été suivi par imagerie in vivo de l'activité luciférase. Les tumeurs primaires des souris, ayant développé des métastases ou non, ont été séquencées, et des analyses génomiques et transcriptomiques menées. La caractérisation des cellules CD45+ a été réalisée par cytométrie en flux spectrale sur les tumeurs primaires, les sites secondaires (tissu pulmonaire), la moelle osseuse et le sang, avant et après l'implantation tumorale, afin de mieux comprendre les différents microenvironnements associés.Résultats : Une différence significative dans l'apparition des métastases a été observée entre souris porteuses de tumeurs MSS et MSI (100 % contre 82,3 %, p = 0,0456). De plus, les souris présentant des métastases MSI ont montré un développement métastatique moins prononcé à certains sites par rapport aux souris MSS. Le séquençage de l'exome complet (WXS) a révélé que la charge mutationnelle tumorale (mutations non-synonymes/megabase), les indels, ainsi que le MSIscore (pourcentage de microsatellites instables) étaient plus élevés dans les tumeurs MSI comparées aux MSS, mais ces différences n'expliquent pas l'écart de développement métastatique. Les analyses transcriptomiques ont mis en évidence que les tumeurs MSS expriment des programmes associés à la transition épithélio-mésenchymateuse (EMT), tandis que les tumeurs primaires MSI et les tumeurs métastatiques MSI étaient respectivement enrichies en signatures prolifératives et immunitaires. Il est à noter que les tumeurs métastatiques MSI étaient spécifiquement enrichies d'une signature hybride EMT, un indicateur d'agressivité tumorale. Par ailleurs, la cytométrie spectrale a permis d'identifier des populations spécifiques de macrophages et de neutrophiles associés aux tumeurs MSI (TAMs-MSI et TANs-MSI) tant dans les tumeurs primaires que sur les sites métastatiques. Enfin, nous avons découvert que l'infiltration de TANs-MSI (mais pas de TAMs-MSI) au niveau des sites secondaires précédait le développement métastatique et pourrait contribuer à la formation d'une niche pré-métastatique spécifique au MSI.Conclusion : Nous avons établi un modèle de cancer métastatique MSI, reproduisant les caractéristiques principales de la maladie, telles qu'une accumulation de mutation et d'indels élévé, ainsi qu'un potentiel métastatique diminué. Nos résultats montrent que la progression métastatique dans ce modèle MSI est associée à une réduction de l'activité immunitaire à la tumeur primaire, et que les tumeurs métastatiques MSI présentent un enrichissement en signatures prolifératives et en signatures hybrides EMT, pouvant ainsi expliquer le mauvais pronostic observé après récidive chez les patients. De plus, ce modèle a mis en lumière des populations myéloïdes spécifiques aux tumeurs MSI ainsi qu'une niche pré-métastatique potentielle liée au MSI. Ce modèle constitue ainsi un outil précieux pour la recherche fondamentale et translationnelle sur le cancer métastatique MSI, tout en apportant de nouvelles perspectives sur les interactions entre le développement métastatique et le phénotype MSIBackground: It is established that mismatch repair deficient (MMR-D), hypermutated and microsatellite instable (MSI) colorectal cancer (CRC) is less prone to metastasis, and has worse prognosis after recurrence, than microsatellite stable (MSS) CRC. The mechanisms behind both these phenomena are still elusive, mainly due to the lack of a good in vivo model of metastatic MSI cancer.Methods: We generated Msh2 knockouts in the luciferase expressing breast cancer cell line 4T1luc+. The MMR-D phenotype, an accumulation of point mutations genome-wide and insertion-deletion (indels) at microsatellite sites, was established by serial passages in vitro before orthotopic injection in the lower left mammary fat pad of BALB/c mice. Metastasis development was assessed through in vivo imaging of luciferase activity. Primary tumors of mice bearing metastasis, or not, were sequenced, and genomic and transcriptomic analysis were performed. Spectral flow cytometry of CD45+ cells was carried out on primary tumors, secondary site (lung tissue), bone marrow and blood before and after tumor engraftment, to characterize the different microenvironments.Results: A significant difference in metastasis occurrence was noted between the MSS and MSI tumor-bearing mice (100% vs 82.3%, p = 0.0456). Moreover, MSI metastatic mice exhibited less site-specific metastatic development compared to their MSS counterparts. Whole exome sequencing (WXS) revealed that tumor mutation burden (TMB, non-synonymous mutations/megabase), indels, and MSIscore (percentage of instable microsatellites) were elevated in the MSI tumors compared to MSS, but did not explain the difference in metastasis occurrence. Transcriptomic analyses demonstrated that MSS tumors express epithelial-mesenchymal transition (EMT) related programs, while MSI metastatic and MSI localized primary tumor were enriched in proliferative and immune related signatures, respectively. Interestingly, MSI metastatic tumor were uniquely enriched with a hybrid EMT signature, a marker of cancer aggressiveness. Furthermore, spectral cytometry uncovered MSI-specific populations of tumor-associated macrophages and neutrophils (MSI-TAMs and MSI-TANs) at the primary tumor and metastatic sites. Finally, we discovered that MSI-TANs (but not MSI-TAMs) infiltration at secondary site predate metastatic development, and may participate in the creation of an MSI-specific pre-metastatic niche.Conclusion: We successfully developed a model of MSI metastatic cancer, recapitulating the hallmarks of the disease, namely elevated TMB, indels and MSIscore, as well as decreased metastatic potential. We have shown that metastatic development in our MSI model is associated with lower immune activity at the primary tumor, and that MSI metastatic tumors are enriched in proliferative and hybrid EMT signatures, that may explain the poor prognosis after recurrence in patients. At last, this model unveiled MSI-specific tumor-associated myeloid populations, and a potential MSI pre-metastatic niche. We provide here a model for fundamental and translational research on MSI metastatic disease, and provide insights on the crosstalk between metastasis development and the MSI phenotype
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Bouguyon, Eléonore. "Etude de la signalisation nitrate dépendante du transcepteur NRT1.1 chez Arabidopsis thaliana". Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20081.
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Les plantes sont capables de percevoir dans leur environnement la disponibilité en nitrate (NO3-), un macro-nutriment essentiel. Chez Arabidopsis thaliana, le transporteur de NO3- NRT1.1 constitue un système de perception qui active de nombreuses réponses au NO3-, notamment la régulation de l'expression de gènes et le développement des racines latérales. Dans ce dernier cas, un mécanisme de transduction du signal a été proposé. Celui-ci met en jeu une activité de transport d'auxine par NRT1.1 qui est inhibée par le NO3-. Cependant, le(s) mécanisme(s) moléculaire(s) permettant à NRT1.1 de contrôler un large panel de réponses au NO3- reste(nt) largement inconnu(s). L'objectif de ce travail était donc d'approfondir nos connaissances sur les voies de signalisation du NO3- dépendantes de NRT1.1. Grâce à l'analyse de mutants et de lignées transgéniques exprimant des versions de NRT1.1 présentant des mutations ponctuelles, nous avons pu découpler certaines des réponses NRT1.1-dépendantes et montré que cette protéine peut percevoir/transduire le signal NO3- au travers d'au moins trois mécanismes distincts, possédant des bases structurales différentes au sein de la protéine. D'autre part, ce travail a permis de valider l'hypothèse selon laquelle NRT1.1, en intervenant comme transporteur d'auxine, contrôle directement le développement des racines latérales, et ce indépendamment des autres transporteurs d'auxine qui y sont exprimés. Enfin, nous avons montré qu'en plus de sa régulation transcriptionnelle déjà connue, NRT1.1 est soumis à une puissante et complexe régulation post-transcriptionnelle. En effet, le transcrit NRT1.1 est stabilisé en présence de NO3- dans la racine alors que l'accumulation de la protéine NRT1.1 est réprimée par le NO3- spécifiquement au niveau des primordia de racines latérales. Les résultats obtenus au cours de ce travail ont permis d'élaborer un modèle cohérent du rôle de signalisation joué par NRT1.1, et ouvrent de nombreuses perspectives pour comprendre comment, chez les plantes, un « transcepteur » (transporteur/senseur) peut contrôler une vaste gamme de réponses adaptatives aux facteurs de l'environnementPlants are able to sense the external availability of nitrate (NO3-), a major macro-nutrient. In Arabidopsis thaliana, the NO3- transporter NRT1.1 acts as a sensor that triggers many different adaptive responses, including the regulation of gene expression and lateral root development. In the latter case, a transduction mechanism that involves a NO3--inhibited auxin transport activity dependent of NRT1 has been proposed. However, the molecular mechanism(s) allowing NRT1.1 to control such a large palette of NO3- responses is still largely unknown. Thus the aim of this work was to better understand and characterize the NRT1.1-dependent NO3- signaling pathway(s). Using mutants and transgenic lines expressing point mutated forms of NRT1.1, we uncoupled several of the NRT1.1-dependent responses and thus demonstrated that NR1.1 can sense/transduce NO3- signal through at least three distinct mechanisms at the protein level. This work also largely confirmed the hypothesis that NRT1.1 directly controls lateral root development through its auxin transport activity regardless of the other auxin transporters expressed in lateral root primordia. Finally, we showed that, besides the already well characterized transcriptional NO3--dependent regulation of NRT1.1, this gene is also subjected to complex post-transcriptional regulations. Indeed, on the one hand, NRT1.1 mRNA is stabilized by NO3- in roots whereas, on the other hand, protein accumulation is specifically repressed by NO3- in lateral root primordia. Altogether, these results allowed us to build a comprehensive model of the complex NRT1.1 signaling and open many perspectives to understand how plant “transceptors” (transporter/sensor) can monitor a large variety of adaptive responses to environmental factors
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King, Eoghan. "Caractérisation phénotypique et moléculaire de la réponse du riz au cours de l’interaction avec des espèces de Burkholderia s.l". Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTG079.
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Dans les conditions naturelles, les plantes interagissent avec une grande diversité de microorganismes, entretenant avec elles des types d’interactions variées allant du mutualisme à la pathogénie. Quelque soit le type d’interaction mis en place, les plantes sont capables de reconnaitre des motifs moléculaires microbiens conservés qui induisent l’activation d’une réponse immunitaire dite « non-hôte ». Cette réponse immunitaire basale a largement été étudiée dans le cas des interactions avec des microorganismes mutualistes et pathogènes. Cependant, dans le cas des « symbioses associatives » avec des rhizobactéries ou des bactéries endophytes bénéfiques, regroupées sous le terme de Plant Growth-Promoting Rhizobacteria (PGPR), les réponses immunitaires et physiologiques des plantes ont très peu été décrites. Dans ce contexte, ce projet de thèse a eu pour objectif de décrire les régulations transcriptionnelles de la monocotylédone modèle, le riz, en réponse à l’interaction avec des bactéries bénéfiques -rhizosphériques ou endophytes- et pathogènes du genre Burkholderia sensu lato (s.l.). Ce genre ubiquiste de béta-protéobactéries a la particularité d'avoir été subdivisé en deux genres aux écologies distinctes : le genre Paraburkholderia regroupant des espèces environnementales et bénéfiques des plantes, et le genre Burkholderia sensu stricto (s.s.) qui regroupe des espèces opportunistes et pathogènes de l'homme ainsi que des pathogènes de plantes, mais aussi des espèces phytobénéfiques (comme B. vietnamiensis). L’analyse par RNA-Seq de la réponse transcriptomique du riz à trois souches endophytes, Paraburkholderia kururiensis M130, Burkholderia vietnamiensis TVV75 et Paraburkholderia phytofirmans PsJN, ont permis de mettre en évidence des régulations physiologiques contrastées en fonction de la souche inoculée. De plus, des analyses comparatives de la colonisation des tissus racinaires par ces souches ont pu associer certaines de ces régulations à différents modes de colonisation. Enfin, l’expression de gènes impliqués dans la réponse immunitaire des plantes, identifiés par l’analyse fonctionnelle des transcriptomes, a été mesurée au cours de cinétiques d’interaction avec une plus large diversité de souches. Pour cela, dix souches de Burkholderia s.l., comprenant trois souches pathogènes, ainsi que trois souches PGPR modèles du riz des genres Azospirillum, Herbaspirillum et Pseudomonas ont été choisies. Cette dernière approche a permis de mettre en évidence des régulations transcriptionnelles associées à des types de colonisation, rhizosphérique et endophytique, ou d’interactions, bénéfiques et délétères. Ces travaux s’intègrent dans la caractérisation des bases moléculaires de la réponse des plantes aux microorganismes bénéfiques qui représentent un potentiel important pour le développement de solutions agronomiques durables favorisant la nutrition et la résistance des plantes aux maladiesIn natural conditions, plants interact with a large diversity of microorganisms maintaining with them various types of interaction ranging from mutualism to pathogenesis. Whatever the type of interaction established, the plants are able to recognize conserved microbial molecular motifs which trigger a so-called “non-host” immune response when perceived. This basal immune response has been extensively studied in the case of interactions with mutualistic and pathogenic microorganisms. However, in the case of “associative symbiosis” with beneficial rhizobacteria or bacterial endophytes, grouped under the term Plant Growth-Promoting Rhizobacteria (PGPR), the immune and physiological responses of plants have been scarcely described. In this context, this thesis project aimed at describing the transcriptional regulations of the model monocotyledonous rice, in response to the interaction with beneficial -rhizospheric or endophytic- and pathogenic bacteria of the genus Burkholderia sensu lato (s.l.). This ubiquitous genus of beta-proteobacteria has the particularity of having been subdivided into two genera with distinct ecologies: the genus Paraburkholderia, which groups together environmental and plant-associated species, and the genus Burkholderia sensu stricto (s.s.), which groups together human opportunistic and pathogenic species but also phytobeneficial species such as B. vietnamiensis. RNA-Seq analysis of the transcriptomic response of rice to three endophytic strains, Paraburkholderia kururiensis M130, Burkholderia vietnamiensis TVV75 and Paraburkholderia phytofirmans PsJN, revealed contrasting physiological regulations depending on the inoculated strain; in addition, comparative analyses of root tissue colonization by these strains enabled to associate some of these regulations with different colonization patterns. Finally, the expression of genes involved in the immune response of plants, identified by the functional analysis of transcriptomes, was measured during interaction kinetics with a wider diversity of strains. For this, ten strains of Burkholderia s.l., comprising three pathogenic strains, as well as three model rice PGPR strains of the genera Azospirillum, Herbaspirillum and Pseudomonas were selected. This last approach highlighted transcriptional regulations associated with the types of colonization, rhizospheric and endophytic, or interaction, beneficial and deleterious.This work is part of the characterization of the molecular bases of plants’ response to beneficial microorganisms which represent an important potential for the development of sustainable agronomic solutions favoring nutrition and plant resistance to diseases
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Nociti, Ricardo Perecin. "Transcrição em embriões bovinos produzidos in vitro /". Jaboticabal, 2018. http://hdl.handle.net/11449/157385.
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Orientador: Vera Fernanda Martins Hossepian de LimaResumo: O processo transcricional em embriões extremamente complexo, nosso trabalho estimou o impacto de perturbações nos processos de transcricionais, durante as fases de ativação do genoma embrionário sobre o desenvolvimento embrionário in vitro de embriões; analisamos dados de sequenciamento de rna (RNA-seq) depositados nos bancos públicos (GEO) desde o estágio de oóocito até o dia 19 do desenvolvimento embrionário; Isolamos e caracterizamos a massa celular interna (ICM) e a trofectoderma (TE) do sexo masculino e feminino, oriundos de um mesmo blastocisto produzido in vitro com espermatozoides sexados (X e Y) e com sêmen convencional e caracterizamos e exploramos o transcriptoma desses isolados celulares. Concluímos então que a EGA menor é essencial para o desenvolvimento embrionário bovino, blastocistos possuem a maior atividade transcricional de um total de 6457 genes diferentemente expressos entre os contrastes avaliado encontramos; 2065 genes diferencialmente expressos entre a ICM e a TE, enquanto a ICM está voltada para a manutenção da pluripotência, a TE está voltada ao metabolismo energético. Os nossos dados sugerem que os embriões fêmeas são mais sensíveis ao cultivo in vitro.
Abstract: Transcription process in embryos is a complex process, our work estimated the impact of perturbations in the transcriptional processes during genome activation of vitro produced bovine embryos on their development; we analyzed public data (GEO) from rna sequencing data (RNA-seq) of oocyte up to the 19th day of embryonic development; We’d performed isolation and characterization of male and female inner cell mass (ICM) and trofectoderma (TE) from the same blastocyst produced in vitro with sorted semen (X and Y) and with conventional semen. We did the characterization and exploratory analysis of the transcriptome of these cells. We conclude that minor EGA is essential for bovine embryonic development. Blastocysts possess the highest transcriptional activity of 6457 differentially expressed genes among analyzed contrasts. We found 2065 genes differentially expressed between ICM and TE, while ICM is maintaining pluripotency, TE is focused on energy metabolism. Our data suggest that female embryos are more sensitive to in vitro culture.
Doutor
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Patin, Constance. "Exploration du dialogue entre le microbiote intestinal et l'hôte chez les enfants nés grands-prématurés à un mois de vie via des méthodes méta-omiques". Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASQ045.
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La naissance prématurée (<37 semaines de gestation) est la principale cause de décès chez les enfants de moins de 5 ans dans le monde. Par conséquent, il est important de comprendre ses conséquences à court et à long terme. Alors que l'association entre la naissance prématurée et la santé à court terme a été largement étudiée, son association avec les résultats à long terme est peu connue. Chez les nourrissons prématurés et très prématurés, le microbiote intestinal est très variable et représente souvent le microbiote trouvé dans l'environnement de l'unité de soins intensifs néonatals.L'objectif de ce travail était de mieux comprendre les interactions entre les profils du microbiote intestinal et l'hôte à l'âge d'un mois chez les nourrissons très prématurés (<32 semaines de gestation ; cohorte EPIPAGE2). Les nourrissons ont été regroupés en fonction des résultats du questionnaire d'âge et d'étape de développement (ASQ) à l'âge de 2 ans.Nous avons réalisé une étude méta-omique sur des échantillons de selles de nourrissons très prématurés à l'âge d'un mois et intégré des données sur le microbiote fécal (séquençage du gène codant l'ARNr 16S), le métabolome (spectrométrie de masse en tandem LC-MS) et le transcriptome de l'hôte (RNA-seq et RT-qPCR).Chez les nourrissons nés grand-prématurés, il est possible de relier des profils de microbiote à différentes voies métaboliques ainsi qu'à des marqueurs immunitaires de l'hôte. Ces combinaisons sont elles-mêmes associées à des évolutions cliniques telles que le transit intestinal ou le neurodéveloppement ultérieur. Le microbiome à 1 mois pourrait être un indicateur non invasif de l'immaturité intestinale. Escherichia et Staphylococcus se sont avérés être les meilleurs indicateurs de maturité et d'immaturité, respectivement. Escherichia pourrait faciliter le processus de maturation intestinale chez les nourrissons prématurésPreterm birth (<37 gestational age) is the leading cause of death in children under 5 years of age worldwide. Therefore, it is important to understand its short-term and long-term consequences. While the association between preterm birth and short-term health has been extensively studied, its link to long-term outcomes remains relatively unknown. In premature and very premature infants, the intestinal microbiota is highly variable and often resembles the microbiota found in the neonatal intensive care unit environment.The aim of this study was to gain a better understanding of the interactions between intestinal microbiota profiles and the host at one month of age in very preterm infants (<32 weeks of gestation; EPIPAGE2 cohort). Infants were grouped based on the results of the Ages and Stages Questionnaire (ASQ) at the age of 2 years, focusing on developmental milestones.We performed a meta-omic study on fecal samples from very-preterm infants at 1 month of age and integrated data on the fecal microbiota (16S rRNA gene sequencing), metabolome (LC-MS), and host transcriptome (RNA-seq).In infants born very prematurely, it is possible to link microbiome profiles to various metabolic pathways as well as host immune markers. These combinations are themselves associated with clinical outcomes such as intestinal transit or later neurodevelopment. The microbiome at 1 month may serve as a non-invasive indicator of intestinal immaturity. Escherichia and Staphylococcus have proven to be the best indicators of maturity and immaturity, respectively. Escherichia might facilitate the process of intestinal maturation in preterm infants
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Jousset, Agnès. "analyse génomique et transcriptomique de bactéries productrices de carbapénèmases". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS527.
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Le combat contre les infections bactériennes reste un enjeu majeur de santé publique notamment avec la dissémination des Entérobactéries productrices de carbapénèmases, capables d’hydrolyser l’ensemble des β-lactamines. On assiste à l’émergence de certains clones épidémiques, se distinguant par leur distribution mondiale, leur forte transmissibilité et leur capacité à persister chez les patients. L’exemple le plus parlant est le cas du clone de Klebsiella pneumoniae appartenant au « sequence type » (ST) 258 et responsable de la diffusion mondiale de la carbapénèmase KPC (Klebsiella Pneumoniae Carbapenemase) portée majoritairement par des plasmides de la famille InFIIk. Les raisons du succès de ce clone et de l’association KPC/IncFIIk/ST258 ne sont pas encore totalement élucidées. Par ailleurs, il n’existe pas de corrélation entre le niveau d’expression d’une carbapénèmase, la sensibilité in vitro de la souche vis à vis des carbapénèmes et l’efficacité clinique d’un traitement par ces molécules. Les phénomènes d’héterorésistance aux carbapénèmes sont fréquents chez les souches produisant KPC, mais l’impact clinique est inconnu. Les mécanismes de régulation de l’expression des carbapénèmases ne sont pas élucidés.Les objectifs de cette thèse résident dans l’analyse des facteurs génétiques associés à la diffusion et la persistance de clones multi-résistants ainsi que l’analyse de l’expression des β-lactamases associées.La première partie de ce travail porte sur l’analyse de l’évolution in vivo d’une souche de K. pneumoniae ST258 produisant KPC ayant persisté chez un patient pendant près de 5 ans. L’analyse comparative des génomes provenant de 17 isolats a permis de mettre en évidence une diversification génétique importante ainsi que la sélection de mutations modifiant la virulence de la souche et sa sensibilité aux antibiotiques. Afin de caractériser les raisons du succès de certains plasmides portant KPC, une analyse transcriptomique d’une souche de Escherichia coli TOP10 transformée par un plasmide multi-réplicon IncFIIk-IncFIB exprimant KPC-2, a été réalisée en présence ou non d’imipénème. Les gènes les plus exprimés dans ces conditions sont les gènes de résistance aux antibiotiques et certains gènes essentiels à la réplication du plasmide. La présence d’imipénème affecte peu la transcription des gènes plasmidiques mais induit un stress oxydatif important dans l’ensemble de la souche. Par ailleurs, l’analyse de l’expression du gène blaKPC-2 dans différentes espèces par 5’-RACE a permis de révéler que ce gène de résistance est sous la dépendance de plusieurs promoteurs, dont la force diffère selon le fond génétique. Cette caractéristique pourrait expliquer le succès de certains isoformes du transposon Tn4401 permettant une meilleure expression du gène blaKPC-2, dans certaines espèces. Les outils développés dans cette thèse ont également été appliqués à l’analyse d’un clone d’Enterobacter kobei ST125 dont la céphalosporinase naturelle ACT-28 possède une activité d’hydrolyse accrue vis à vis de l’imipénème. Enfin, l’analyse du génome de la première souche Shewanella sp. produisant une BLSE de type CTX-M-15 a permis de révéler la présence d’un nouveau variant oxacillinase chromosomique avec activité carbapénèmase, appelé OXA-535. OXA-535 est proche d’OXA-436, un autre variant carbapénèmase porté par un plasmide ayant déjà disséminé chez les Entérobactéries. L’analyse de l’environnement génétique des gènes blaOXA-535 et blaOXA-436 confirme le rôle du genre Shewanella comme progéniteur des carbapénèmases de classe D. Ce travail contribue à une meilleure compréhension de la diffusion de certains clones multi-résistants et des mécanismes contrôlant l’expression des gènes de résistance aux β-lactaminesMultidrug resistant bacteria and in particular carbapenemase-producing Enterobacteriaceae remain a major health public challenge. Some successful clones are emerging globally, due to their high transmissibility and their ability to colonize and persist in patients over time. Genomic analyses revealed that the dissemination of KPC carbapenemase is closely related to the spread of Klebsiella pneumoniae of the sequence-type (ST) 258 and to few successful plasmids linked to IncFIIk family. However, the reasons of the association between K. pneumoniae ST258, IncFIIk plasmids and KPC that led to the rapid spread of this clone are currently unknown.Furthermore, there is no correlation between expression level of a carbapenemase-encoding gene, in vitro susceptibility to carbapenems and efficiency of a carbapenem-based treatment. Most of the time, KPC-producing K. pneumoniae exhibit a heteroresistant phenotype with carbapenems, but its clinical impact remains unknown. The mechanisms underlying the regulation of carbapenemases expression remain to be explored.The objectives of the thesis are to obtain deeper insights into genomic plasticity of carbapenemase–producing clones, and into the expression of their β-lactamases.The first part of this work was dedicated to the in vivo evolution of a single strain of KPC-producing K. pneumoniae ST258 that colonized a patient for almost 5 years. Genomic comparison of 17 isolates revealed a remarkable diversification with occurrence of several mutations with impact on bacterial virulence and susceptibility to antibiotics.Several studies extensively described the genetic structures of blaKPC-carrying plasmids, but information regarding gene expression at the whole plasmid level are lacking. Accordingly, we performed RNA-seq on Escherichia coli TOP10 transformed with an IncFIIk-IncFI blaKPC-2-carrying plasmid, with or without imipenem exposure. In both conditions, plasmid-encoded genes related to antimicrobial resistance and involved in plasmid replication were the most expressed. Imipenem exposure led to a more general response with overexpression of E. coli numerous chromosome-encoded genes involved in oxidative stress response. In addition, analysis of blaKPC-2 gene expression in several species using 5’RACE revealed the presence of several promoters whose strength depends on the bacterial genetic background. This could promote higher expression of blaKPC-2 gene and explain the association of some isoforms of Tn4401 in different species. The tools developed in the frame of this work were also applied to study a single Enterobacter kobei ST125 clone whose natural cephalosporinase (ACT-28) has increased hydrolytic activity towards imipenem. Finally, genomic analysis of the first ESBL-producing Shewanella sp. was performed. It revealed the presence of blaCTX-M-15 and blaSHV-2 genes carried on an IncA/C plasmid and a new chromosomally-encoded oxacillinase variant of OXA-48 with carbapenemase activity, called OXA-535. OXA-535 was found to be closely related to OXA-436, another carbapenemase which has recently spread in Enterobacteriaceae. Analysis of the genetic environment of both blaOXA-48-like genes confirmed the role of Shewanella spp. as progenitors of class D carbapenemases.Overall, this work contributes to a better comprehension of the diffusion of multi-drug resistant clones and of the mechanisms implicated in β-lactamase expression
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Gay, Elise. "Dissection transcriptomique de la biologie de Leptosphaeria maculans lors de ses interactions avec son hôte (le colza) et avec un membre du complexe d'espèces, Leptosphaeria biglobosa Large-scale transcriptomics to dissect two years of the life of a fungal phytopathogen interacting with its host plant". Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASB015.
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Leptosphaeria maculans est un champignon pathogène responsable de la nécrose du collet chez le colza. Son cycle de vie est long et complexe car composé d’une succession d’étapes de colonisation asymptomatiques puis nécrotiques des différents tissus de l’hôte, depuis la colonisation hémibiotrophe des feuilles à l’automne à la nécrose du collet au printemps. Après ces phases infectieuses dans des tissus végétaux vivants, L. maculans vit en tant que saprophyte dans les résidus de culture. Jusqu’ici, l’étude des déterminants moléculaires de la pathogénie chez L. maculans s’est concentrée sur l’analyse d’une classe spécifique de gènes, codant pour des « effecteurs », et cela durant une seule partie du cycle : l’infection précoce des feuilles. A l’heure actuelle il n’y a pas de vue d’ensemble des gènes impliqués dans la pathogénie durant tout le cycle infectieux. Aussi, le cycle de vie de L. maculans est intimement lié à celui de Leptosphaeria biglobosa, une espèce proche mais moins pathogène. L. biglobosa coinfecte le colza avec L. maculans durant tout leur cycle de vie, mais son impact sur L. maculans est mal connu. Récemment, 420 échantillons biologiques, collectés durant toutes les étapes du cycle de vie de L. maculans, ont été séquencés par RNA-Seq. Ils incluent des conditions in vitro et in planta, à la fois dans un environnement contrôlé (en coinfection ou non avec L. biglobosa) et en conditions d’infection naturelle. Les objectifs de ma thèse étaient : (i) d’identifier le plus exhaustivement possible, par des approches transcriptomiques, les gènes induits chez L. maculans durant l’entièreté de son cycle infectieux et (ii) de déterminer l’impact de l’interaction biotique avec L. biglobosa. J’ai d’abord montré que 9 % des gènes prédits chez L. maculans sont induits spécifiquement lors de l’infection. Ils sont répartis en huit vagues d’expression redécoupant le cycle tel que décrit dans la littérature et révèlent, pour certains stades, une décomposition transcriptomique encore plus complexe, qui dépend de l’organe colonisé ou du type trophique adopté par le champignon. Je démontre aussi l’importance de la régulation épigénétique puisque toutes les vagues d’expression sont enrichies en gènes localisés dans un environnement génomique de type hétérochromatinien. Lorsque le troisième partenaire, L. biglobosa, entre en jeu en début de cycle, l'expression des gènes chez L. maculans stagne et est accompagnée de l’arrêt de la colonisation. Cet effet inhibiteur est cependant restreint à des conditions de co-inoculations rarement observées lors des infections naturelles. Mon projet de thèse constitue ainsi une première description transcriptomique du cycle de vie de L. maculans dans son intégralité et en interaction avec son environnement biotiqueLeptosphaeria maculans is a pathogenic fungus responsible for the stem canker disease of oilseed rape. Its life cycle is long and complex and is composed of a succession of asymptomatic and necrotic colonisation stages of the host tissues, from the hemibiotrophic colonisation of leaves in autumn to the stem canker development in spring. After these infectious stages on living plant tissue, L. maculans survives as a saprophyte within crop residues. So far, the study of the molecular determinants of L. maculans pathogenesis was focused on a specific class of genes, encoding "effector" proteins, and focused on the early infection on leaves. At present there is no global view of the genes involved in the pathogenesis during the entire infection cycle. In addition, the life cycle of L. maculans is closely related to that of Leptosphaeria biglobosa, a closely related, less pathogenic species. L. biglobosa co-infects the oilseed rape plants along with L. maculans throughout the fungal life cycles, but its impact on L. maculans is poorly understood. Recently, 420 biological samples, collected during all stages of the life cycle of L. maculans, have been sequenced by RNA-Seq, including in vitro and in planta conditions, both in controlled environments (whether or not co-infected with L. biglobosa) or under natural infection. The objectives of my thesis were: (i) to identify as exhaustively as possible, using tanscriptomic approaches, the genes induced in L. maculans during its entire infectious cycle and, (ii) to determine the impact of the biotic interaction with L. biglobosa. I first showed that 9% of the predicted genes in L. maculans are induced specifically during infection. These are clustered into eight waves of expression, outlining the cycle as described in the literature and revealing, for some stages, a more complex transcriptomic subdivision, depending on the organ infected or on the lifestyle adopted by the fungus. I also demonstrate the importance of epigenetic regulation since all the waves of expression are enriched with genes located in a heterochromatin environment. When the third partner, L. biglobosa, coinfects the leaves at the beginning of the cycle, the gene expression in L. maculans stagnates and the plant colonisation by L. maculans is inhibited. However, this inhibitory effect is conditioned by strict conditions of co-inoculations, rarely observed during natural infections. My thesis project thus constitutes a first transcriptomic description of the life cycle of L. maculans in its entirety and in interaction with its biotic environment
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Choucair, Fadi. "Exploration du transcriptome spermatique par le séquençage nouvelle génération et le portrait épigénétique de l’infertilité masculine". Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4058.
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L’infertilité masculine est actuellement considérée comme un problème majeur qui pose une situation alarmante sur la santé publique. L’oligozoospermie, l’asthénozoospermie et la tératozoospermie sont les trois anomalies les plus connues des spermatozoïdes. Elles affectent, respectivement, la densité, la motilité et la morphologie des spermatozoïdes. Un spermatozoïde anormal est très souvent corrélé à des altérations génétiques et épigénétiques qui peuvent affecter considérablement le transcriptome. Dans ce sens, le séquençage aléatoire du transcriptome entier des spermatozoïdes ou RNA-seq constitue un outil puissant pour caractériser ces maladies. Jusqu’à présent, il n’existe aucune étude exploitant des données RNA-seq chez des hommes présentant de telles anomalies spermatiques. L’objectif principal de notre étude fût d’identifier des profils distincts des modifications du transcriptome de chaque phénotype d’infertilité pour ainsi révéler des gènes-signatures qui tamponnent une spermatogenèse pathologiquePour ce faire, les transcriptomes des spermatozoïdes de 60 sujets infertiles atteints soit d’oligozoospermie, d’asthénozoospermie ou de tératozoospermie ont été comparés à ceux de 20 patients fertiles. Ces analyses supervisées nous ont conduit à identifier: (i) les gènes clés spécifiques aux différentes anomalies des spermatozoïdes (ii) les voies de signalisation associées, (ii) les différents longs ARNs non codants dérégulés dans ces anomalies. Au niveau de l’oligozoospermie, les transcrits de spermatozoïdes dérégulés étaient associées à divers stades de la spermatogenèse, y compris le cycle cellulaire méiotique, l’assemblage du complexe synaptonémal, la cohésion des chromatides sœurs, les processus métaboliques de piRNA, le processus catabolique protéique dépendant de la voie de l’ubiquitine, à la réponse aux dommages de l'ADN et particulièrement le processus de fécondation. Quant à l’asthenozoospermia, la spermatogenèse, l’assemblage du cil, des voies métaboliques reliées à la spermatogenèse, la chimiotaxie et la physiologie des cellules immunitaires ont été significativement dérégulés. De plus, ce qui nous a intéressé au plus était l’analyse des transcrits sous-exprimés qui a permis l’identification de nombreux transcrits associées aux modifications des histones. Nous avons aussi mis en évidence une sous expression des gènes différentiellement exprimés qui définit la tératozoospermie. Cette sous expression est associée au système ubiquitine-protéasome, à l’organisation du cytosquelette, au cycle cellulaire, à la SUMOylation en réponse aux dommages de l'ADN et aux protéines de réparation ainsi qu’à de nombreux modulateurs épigénétiques. Les gènes signature de l'oligozoospermie ont été liés au processus de fécondation et les composants de la matrice extracellulaire, tandis que ceux de la tératozoospermie sont liés à la spermatogenèse et la morphogenèse cellulaire, alors que les gènes signature de l'asthénozoospermie sont impliqués dans l'assemblage du ribosome et du flagelle. En complément de cette étude, nous avons réalisé une étude très globale du paysage épigénétique du sperme des hommes infertiles. Nous avons, ainsi comparé les niveaux des espèces réactives de l’oxygène (ERO), de méthylation de l’ADN, ainsi que l’intégrité de la chromatine dans les spermatozoïdes de 30 individus infertiles avec ceux de 33 individus fertiles. Nos analyses montrent des niveaux élevés d’ERO chez les individus infertiles. Ces niveaux sont d’une part négativement corrélés avec les niveaux de méthylation globale de l’ADN et d’autre part négativement corrélés avec ceux de la 5-hydroxyméthylcytosine et de la 5-formylcytosine (intermédiaire dans le processus de déméthylation active). Ces derniers suggèrent qu’une infertilité associée au stress oxydatif conditionne l’épigénome du sperme. En conclusion, l’ensemble de notre travail apporte des ressources précieuses et originales dans la compréhension des pathologies de spermeMale infertility is actually considered as a public alarming health problem. The sperm pathologies spectrum ranges between different phenotypes including oligozoospermia, asthenozoospermia and teratozoospermia depending on the sperm conventional parameters abnormalities. Abnormal sperm is characterized by genetic alterations and epigenetic alterations which can affect the transcriptome extensively. These alterations in RNA profiles are retrospectively indicative of aberrant spermatogenic events. RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome. To date, RNA-seq analysis of sperm from infertile men has not been reported. Our objectives are: (i) recognize key clusters, key pathways and specific gene transcripts for different sperm abnormalities; (ii) catalog the spermatozoal lncRNAs in different sperm pathologies; (iii) identify signature genes which are mechanistically important in the cascade of events driving a pathological spermatogenesis; (iii) portray the global epigenetic landscape in sperm from infertile men. Expression data from 60 sperm samples from 3 groups of infertile men (oligozoospermia, asthenozoospermia, and teratozoospermia) were generated on Illumina HiSeq platform, compared to 20 fertiles, and the resulting gene expression patterns were analyzed for functional enrichment. Our supervised analyses identified numerous differentially expressed genes between fertile and infertile men. In oligozoospermia, the deregulated spermatozoal transcripts were associated with various stages of spermatogenesis including meiotic cell cycle, synaptonemal complex assembly, sister chromatid cohesion, piRNA metabolic process, ubiquitin-dependent protein catabolic process, cellular response to DNA damage stimulus and interestingly fertilization. As for asthenozoospermia, spermatogenesis, cilium assembly, metabolic-related pathways, chemotaxis and immune cell physiology were most significantly differentially expressed. Interestingly, numerous transcripts associated with histone modifications were highly down-regulated. With regards to teratozoospermia, we evidenced sperm-specific differentially expressed genes which are involved in the ubiquitin-proteasome, cytoskeleton organization, the cell cycle pathway, SUMOylation of DNA damage response and repair proteins, as well as many putative epigenetic modulators of gene expression.. We also attempted to identify distinct patterns of gene expression changes that were definite to the different abnormal sperm phenotypes in infertile men relative to controls. Signature genes of oligozoospermia were over-enriched by genes involved in fertilization and extracellular matrix components, while signature genes of teratozoospermia were enriched by genes involved in spermatogenesis and cellular components involved in morphogenesis, whilst signature genes of asthenozoospermia were enriched by genes implicated in ribosome and cilium assembly.We complemented this work by a parallel epigenetic analysis of the global epigenetic landscape in infertile men. We compared the levels of reactive oxygen species (ROS), DNA integrity and global epigenetic parameters in sperm from 33 infertile subjects with abnormal semen parameters compared to fertile individuals. We pointed out that infertile men are characterized by strikingly high levels of reactive oxygen species (ROS) which were in part negatively correlated with the global DNA methylation, and positively correlated with the levels of 5-hydroxymethylcytosine and 5-formylcytosine (active demethylation intermediates). These findings suggest that male infertility associated with oxidative stress shapes the sperm epigenetic landscape. In summary, this original work yielded a transcriptional portrait of sperm abnormalities and provided valuable resources that would further elucidate sperm pathologies
Książki na temat "Transcriptomie"
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Cellerino, Alessandro, i Michele Sanguanini. Transcriptome Analysis. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1.
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Wang, Yejun, i Ming-an Sun, red. Transcriptome Data Analysis. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7710-9.
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Azad, Rajeev K., red. Transcriptome Data Analysis. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-3886-6.
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Calogero, Raffaele A., i Vladimir Benes, red. Single Cell Transcriptomics. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2756-3.
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Passos, Geraldo A., red. Thymus Transcriptome and Cell Biology. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-12040-5.
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Bernot, Alain. Genome Transcriptome and Proteome Analysis. New York: John Wiley & Sons, Ltd., 2005.
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Shelomi, M., red. Transcriptomics in entomological research. Wallingford: CABI, 2020. http://dx.doi.org/10.1079/9781789243130.0000.
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Wu, Jiaqian, red. Transcriptomics and Gene Regulation. Dordrecht: Springer Netherlands, 2016. http://dx.doi.org/10.1007/978-94-017-7450-5.
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Passos, Geraldo A., red. Transcriptomics in Health and Disease. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-87821-4.
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Passos, Geraldo A., red. Transcriptomics in Health and Disease. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-11985-4.
Pełny tekst źródłaCzęści książek na temat "Transcriptomie"
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Rotter, Ana, Matjaž Hren, Björn Usadel i Kristina Gruden. "VisualisationVISUALISATION of Transcriptomic TRANSCRIPTOMICS s Data in Metabolic Pathways". W Methodologies and Results in Grapevine Research, 335–42. Dordrecht: Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-90-481-9283-0_23.
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Cellerino, Alessandro, i Michele Sanguanini. "A primer on data distributions and their visualisation". W Transcriptome Analysis, 1–10. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_1.
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Cellerino, Alessandro, i Michele Sanguanini. "Next-generation RNA sequencing". W Transcriptome Analysis, 11–25. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_2.
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Cellerino, Alessandro, i Michele Sanguanini. "RNA-seq raw data processing". W Transcriptome Analysis, 27–44. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_3.
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Cellerino, Alessandro, i Michele Sanguanini. "Differentially expressed gene detection and analysis". W Transcriptome Analysis, 45–58. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_4.
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Cellerino, Alessandro, i Michele Sanguanini. "Unbiased clustering methods". W Transcriptome Analysis, 59–83. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_5.
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Cellerino, Alessandro, i Michele Sanguanini. "Knowledge-based clustering methods". W Transcriptome Analysis, 85–98. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_6.
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Cellerino, Alessandro, i Michele Sanguanini. "Network analysis". W Transcriptome Analysis, 99–119. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_7.
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Cellerino, Alessandro, i Michele Sanguanini. "Mesoscale transcriptome analysis". W Transcriptome Analysis, 121–39. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_8.
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Cellerino, Alessandro, i Michele Sanguanini. "Microscale transcriptome analysis". W Transcriptome Analysis, 141–68. Pisa: Scuola Normale Superiore, 2018. http://dx.doi.org/10.1007/978-88-7642-642-1_9.
Pełny tekst źródłaStreszczenia konferencji na temat "Transcriptomie"
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Collar, Giovanna Carello, Marco Antônio De Bastiani i Eduardo R. Zimmer. "HUNTINGTON’S DISEASE AND EARLYONSET ALZHEIMER’S DISEASE SHARE A TRANSCRIPTOMIC SIGNATURE". W XIII Meeting of Researchers on Alzheimer's Disease and Related Disorders. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1980-5764.rpda082.
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Background: Neurodegenerative diseases share progressive loss of neurons and protein misfolding, which ultimately culminates in dementia; many diseases have been identified as causes of early-onset dementia (< 65 years of age) such as Huntington’s disease (HD) and early-onset Alzheimer’s disease (EOAD). Importantly, disease-specific genetic mutations have already been identified for HD and EOAD. Thus, one could suggest that the molecular link between these diseases may arise from alterations at the transcriptomic level, which is yet to be determined. Objective: We aimed at identifying transcriptome similarities between HD and EOAD. Methods: We collected data of the postmortem cerebral cortex from 1 HD and 6 AD microarray studies in the Gene Expression Omnibus. Of note, only subjects with age at death under 65 were selected (HD: n = 158, controls: n = 158; EOAD: n = 65, controls: n = 266). Differential expression and functional enrichment analyses were performed. Results: We identified 1,260 differentially expressed genes and 675 enriched gene ontology terms between HD and EOAD. Conclusion: Our results demonstrate a transcriptomic signature shared by HD and EOAD. Unveiling the similarities between these diseases at the transcriptomic level could advance our knowledge about pathogenesis and may help to develop therapeutic strategies targeting early-onset dementias.
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Mazur, O. E., I. A. Kutyrev, T. V. Sidorova, L. V. Sukhanova, N. B. Terenina i S. O. Movsesyan. "TRANSCRIPTOME ANALYSIS OF THE SPLEEN OF THE BAIKAL CISCO (LAKE BAIKAL, EASTERN SIBERIA)". W THEORY AND PRACTICE OF PARASITIC DISEASE CONTROL. VNIIP – FSC VIEV, 2024. http://dx.doi.org/10.31016/978-5-6050437-8-2.2024.25.251-255.
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For the first time, new data have been presented on the spleen transcriptome of the Baikal cisco Coregonus migratorius Georgi, 1775 (Salmoniformes: Coregonidae), infected with parasites of different systematic groups. Transcriptomic libraries were sequenced on an Illumina NextSeq550 sequencer using the NextSeq® 550 High Output Kit v2. The de-novo transcriptome was assembled. Conserved domains and their associated Gene Ontology annotations were predicted with Blast2Go. The annotation results of the obtained transcripts found that transcripts were distributed in the spleen into the following categories: molecular functions, biological processes, and cellular components. Among the molecular functions, transcripts of enzyme binding (25.8%), transferase activity (24.7%), hydrolase activity (24.4%), catalytic activity affecting proteins (22.2%), and DNA binding (21%) predominated. Biological processes were dominated by transcripts of cellular processes (46.7%), metabolic processes (38.6%), biological regulation (38.2%), and regulation components of biological processes (36.6%). The category of cellular GO components identified terms, namely cytoplasmic vesicles (25.9%), cytoplasmic membranes (23.1%), nucleoplasm (22.1%), cytoskeletal part (18.6%), cytosol and cellular compounds (17%) in a greater extent.
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Mazur, O. E., I. A. Kutyrev, T. V. Sidorova i L. V. Sukhanova. "TRANSCRIPTOME ANALYSIS OF INTESTINES OF THE BAIKAL OMUL (LAKE BAIKAL, EASTERN SIBERIA)". W THEORY AND PRACTICE OF PARASITIC DISEASE CONTROL. All-Russian Scientific Research Institute for Fundamental and Applied Parasitology of Animals and Plant – a branch of the Federal State Budget Scientific Institution “Federal Scientific Centre VIEV”, 2023. http://dx.doi.org/10.31016/978-5-6048555-6-0.2023.24.268-274.
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New data were presented for the first time on the intestinal transcriptome of the
intestines (posterior section) of the Baikal omul Coregonus migratorius Georgi, 1775
(Salmoniformes: Coregonidae) belonging to the deep water bottom morphological
group (Lake Baikal) infected with parasites of various systematic groups: cestodes
Dibothriocephalus dendriticus, Proteocephalus longicollis, Eubothrium crassum, and
nematode Contracaecum osculatum baicalensis. Sequencing of the transcriptomics
libraries was performed on an Illumina NextSeq550 sequencer using the NextSeq®
550 High Output Kit v2. Based on the obtained data, de-novo transcriptome assembly was performed. Conserved domains and their associated Gene Ontology
annotations were predicted using Blast2Go. As a result, it was found that in the posterior section of the intestine enriched with lymphoid tissue (GALT), expression
of functional proteins was observed that were primarily associated with enzymatic
activity, with the development of specialized tissues, with cellular, metabolic and
secretory processes. It should be noted that a significant proportion of gene ontology
terms is associated with the functioning of the immune system, and with the cellular
response to stress, which, under conditions of sensitization by the metabolic end
products of helminths and their traumatic and antigenic effects, is quite understandable. The identified transcriptome may provide new information for understanding
the functions of lymphoid organs in salmonids with parasitosis.
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"Expression of IPD3, a transcriptional regulator of AM symbiosis, affects immunity and flowering time in non-host Arabidopsis". W IS-MPMI Congress. IS-MPMI, 2023. http://dx.doi.org/10.1094/ismpmi-2023-13.
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Arbuscular mycorrhizal symbiosis (AM) is a beneficial trait originating with the first land plants. The ability to host AM has since been lost from diverse plant species. Genes in the Common Symbiosis Pathway that are essential to establish AM hosting were lost from Brassicaceae along with the trait itself, including Interacting Protein of DMI3 (IPD3), a key transcription factor connecting upstream signaling of AM fungal presence to the downstream gene-regulatory network for AM functions. We generated transgenic Arabidopsis plants expressing the DNA-binding domain of IPD3 and used phenotypic and transcriptome analysis to characterize the effect of IPD3 expression in Arabidopsis in the presence and absence of AM fungus Rhizophagus irregularis. We compared these results to the AM-host model Lotus japonicus and its ipd3 knockout mutant cyclops-4. Despite its long history as a non-AM species, restoring IPD3 expression to Arabidopsis significantly altered transcription related to growth and defense, and delayed flowering time. Our comparative transcriptomic results indicate that some genetic connections for IPD3 remain conserved in Arabidopsis despite the long evolutionary time since its loss.
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Luong, Nga, Wei Yan, Jeffrey Lim, Yuezhen Xue, Abu Bakr Azam, Joe Poh Sheng Yeong, Mai Chan Lau i Yiyu Cai. "1288 Spatial transcriptomics-enabled integrated morphology-transcriptome tumor cell phenotyping using machine learning". W SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.1288.
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Sodnomov, T. C., i I. A. Kutyrev. "STUDY ON POTENTIAL IMMUNOREGULATORY PROTEINS IN THE EXCRETORY-SECRETORY PRODUCTS OF CESTODES". W THEORY AND PRACTICE OF PARASITIC DISEASE CONTROL. VNIIP – FSC VIEV, 2024. http://dx.doi.org/10.31016/978-5-6050437-8-2.2024.25.388-393.
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This article studied excretory-secretory products of parasitic flatworms aimed at searching for potential immunoregulatory proteins. Immunoregulatory proteins are poorly studied at the moment. Recent years have showed increased interest in identifying immunoregulatory molecules produced by parasitic worms. Potential immunoregulatory proteins will make a significant contribution to the development of medicine and biotechnology and will make it possible to effectively treat allergic and other autoimmune diseases. The study used methods of bioinformatics, proteomics, and transcriptomics. Potential immunoregulatory proteins were identified in the Ligula interrupta secretome proteins and listed. Each protein was analyzed for possible immunoregulatory functions in the parasite-host system. Based on identification data of SEP proteins using parasite transcriptomes, annotation of secretome proteins (SEP) was made in the NCBI and Swissprot international databases. A table was compiled with identified potential immunoregulatory proteins. A functional analysis of each protein was performed. Protein functions were determined based on analysis of scientific articles, patents and publications. By comparing different proteins, it is possible to identify those that are similar in domain structure, phylogeny, and description. The discovered potential immunoregulatory proteins will make a significant contribution to the development of medicine and biotechnology and will make it possible to effectively treat allergic and other autoimmune diseases.
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BenHamadou1, Alexandra Leitao, Zenaba Khatir, Noora Al-Shamary, Hassan Hassan, Zainab Hizan, Aisha Al-Ashwal, Mark Chatting i in. "Pearl Oyster: From National Icon To Guardian of Qatar's Marine Environment". W Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0051.
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The NPRP9-394-1-090 project “Pearl Oyster: from national icon to guardian of Qatar's marine environment” had as main aim to develop and apply an integrated suite of chemical and biological methods as early warning tools to assess the “health” of Qatar’s marine environment. The central theme consisted in an investigative monitoring program around the use of the pearl oyster, Pictada imbricata radiata, as a sentinel or guardian species. We have characterized the main environmental contaminants of concern at a selected number of sites around the Qatari coast (UmmBab, Al Khor, Al Wakra and Simaisma), during 2 years, in summer and winter. Potential ecological effects of contaminants (targeted and untargeted) were investigated at different biological organization levels (gene, chromosome, cell, individual, population), through a multidisciplinary approach, using classical and genotoxicological endpoints, integrative histopathology and transcriptomic responses to the different environmental stresses. To our knowledge, this is the first time an integrated approach connecting all these disciplines has been applied in the Qatari marine environment. We present here the main results, of this 3 years project, obtained in all different disciplinary approaches. The results of this project will leave a legacy of resources for future Qatari researchers, including an open access transcriptome data base and the first description of common pathologies observed in the pearl oyster P. i. radiata. Moreover, they will also represent a sound science-based baseline data essential for conservation and management planning, by integration of the data from all the different disciplines applied in the project to assess the potential ecological effects of contaminants at different biological levels.
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Angelotti, Austin, Rachel Cole, Amy Webb, Maciej Pietrzak i Martha Belury. "Diet-induced Gene Expression Changes of Cachectic Muscle, Adipose, and Liver". W 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/gvbe2596.
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Cancer cachexia is a systemic disease characterized by muscle and adipose loss that cannot be reversed by increasing caloric intake. Our previous research has shown insulin resistance precedes cancer cachexia in the C26 mouse model of cachexia, and a diet high in linoleic acid, the essential omega-6 polyunsaturated fatty acid, attenuates the C26-induced insulin resistance. Therefore, to better understand how dietary linoleic acid is improving insulin sensitivity, we characterized gene expression changes in three major tissues responsible for controlling insulin sensitivity: skeletal muscle, adipose, and liver. To do this male CD2F1 (Charles River, MA) were randomized to semi-purified diet (24% fat by weight) containing fat prominently from lard, or containing fat prominently from safflower oil (a linoleic acid-rich oil). One week after diet randomization, mice were inoculated with colon-26 (C26) adenocarcinoma cells (1.0E6 cells). 13 days after inoculation mice were euthanized and gastrocnemius skeletal muscle, epididymal white adipose tissue, and liver tissue were collected for total transcriptome analysis using poly-A enriched next generation RNA-sequencing. Differentially expressed genes were selected based on p-values < 0.05. There were no detectable differences in body weight or food intake between the two diets in mice with C26 tumors. Between the two diets 12 genes were differentially expressed in the muscle, while 57 genes were differentially expressed in the liver, and 314 genes were differentially expressed in adipose. A linoleic acid enriched diet had little effect on the skeletal muscle transcriptome but induced larger transcriptome changes in liver and adipose. This could suggest dietary linoleic acid increases insulin sensitivity through affecting metabolism in adipose and liver, rather than skeletal muscle. Determining these diet-induced transcriptome changes allows us to better target tissue-specific molecular mechanisms of linoleic acid in future research.
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Gribchenko, E. S. "The study of transcriptomes of symbiotic tissue of pea using the third-generation sequencing technology Oxford Nanopore". W 2nd International Scientific Conference "Plants and Microbes: the Future of Biotechnology". PLAMIC2020 Organizing committee, 2020. http://dx.doi.org/10.28983/plamic2020.093.
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The transcriptome profiles the cv. Frisson mycorrhizal roots and inoculated nitrogen-fixing nodules were investigated using the Oxford Nanopore sequencing technology. A database of gene isoforms and their expression has been created.
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Brenes, David, Qinghua Han, Kevin Bishop, Adam Glaser i Jonathan T. C. Liu. "An open-top light-sheet (OTLS) microscope for surveying gene expression in thick expanded tissues". W Optics and the Brain. Washington, D.C.: Optica Publishing Group, 2024. http://dx.doi.org/10.1364/brain.2024.bs5c.4.
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We designed a novel non-orthogonal dual-objective open-top light-sheet microscope to resolve individual genomic/transcriptomic targets in thick hydrogel-based expanded fluorescence in situ hybridization labeled tissues at moderate tissue expansions.
Raporty organizacyjne na temat "Transcriptomie"
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Nelson, Peter S. The Single Prostate Cell Transcriptome as Biological Assay. Fort Belvoir, VA: Defense Technical Information Center, marzec 2002. http://dx.doi.org/10.21236/ada401685.
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Nelson, Peter S. The Single Prostate Cell Transcriptome as Biological Assay. Fort Belvoir, VA: Defense Technical Information Center, wrzesień 1999. http://dx.doi.org/10.21236/ada381283.
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Chan, Timothy A. Targeting Master Regulators of the Breast Cancer Metastasis Transcriptome. Fort Belvoir, VA: Defense Technical Information Center, lipiec 2014. http://dx.doi.org/10.21236/ada608859.
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Tien, Ming. Transcriptome and Biochemical Analyses of Fungal Degradation of Wood. Office of Scientific and Technical Information (OSTI), marzec 2009. http://dx.doi.org/10.2172/1056641.
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Merchant, Sabeeha, i Matteo Pellegrini. Genome Annotation and Transcriptomics of Oil-Producing Algae. Fort Belvoir, VA: Defense Technical Information Center, marzec 2015. http://dx.doi.org/10.21236/ada622412.
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Mockler, Todd. A Universal Genome Array and Transcriptome Atlas for Brachypodium Distachyon. Office of Scientific and Technical Information (OSTI), kwiecień 2017. http://dx.doi.org/10.2172/1351713.
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Sun, Hongyan, Peng Liu, Lisa K. Nolan i Susan J. Lamont. Thymus Transcriptome Response to Avian Pathogenic E. coli (APEC) Infection. Ames (Iowa): Iowa State University, styczeń 2015. http://dx.doi.org/10.31274/ans_air-180814-1313.
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Coble, Derrick, Erin Sandford, Tieming Ji i Susan J. Lamont. Impacts of Salmonella Enteritidis Infection on Liver Transcriptome in Broilers. Ames (Iowa): Iowa State University, styczeń 2012. http://dx.doi.org/10.31274/ans_air-180814-57.
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Ghanim, Murad, Joe Cicero, Judith K. Brown i Henryk Czosnek. Dissection of Whitefly-geminivirus Interactions at the Transcriptomic, Proteomic and Cellular Levels. United States Department of Agriculture, luty 2010. http://dx.doi.org/10.32747/2010.7592654.bard.
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Our project focuses on gene expression and proteomics of the whitefly Bemisia tabaci (Gennadius) species complex in relation to the internal anatomy and localization of expressed genes and virions in the whitefly vector, which poses a major constraint to vegetable and fiber production in Israel and the USA. While many biological parameters are known for begomovirus transmission, nothing is known about vector proteins involved in the specific interactions between begomoviruses and their whitefly vectors. Identifying such proteins is expected to lead to the design of novel control methods that interfere with whitefly-mediated begomovirus transmission. The project objectives were to: 1) Perform gene expression analyses using microarrays to study the response of whiteflies (B, Q and A biotypes) to the acquisition of begomoviruses (Tomato yellow leaf curl (TYLCV) and Squash leaf curl (SLCV). 2) Construct a whitefly proteome from whole whiteflies and dissected organs after begomovirus acquisition. 3) Validate gene expression by q-RTPCR and sub-cellular localization of candidate ESTs identified in microarray and proteomic analyses. 4) Verify functionality of candidate ESTs using an RNAi approach, and to link these datasets to overall functional whitefly anatomical studies. During the first and second years biological experiments with TYLCV and SLCV acquisition and transmission were completed to verify the suitable parameters for sample collection for microarray experiments. The parameters were generally found to be similar to previously published results by our groups and others. Samples from whole whiteflies and midguts of the B, A and Q biotypes that acquired TYLCV and SLCV were collected in both the US and Israel and hybridized to B. tabaci microarray. The data we analyzed, candidate genes that respond to both viruses in the three tested biotypes were identified and their expression that included quantitative real-time PCR and co-localization was verified for HSP70 by the Israeli group. In addition, experiments were undertaken to employ in situ hybridization to localize several candidate genes (in progress) using an oligonucleotide probe to the primary endosymbiont as a positive control. A proteome and corresponding transcriptome to enable more effective protein identification of adult whiteflies was constructed by the US group. Further validation of the transmission route of begomoviruses, mainly SLCV and the involvement of the digestive and salivary systems was investigated (Cicero and Brown). Due to time and budget constraints the RNAi-mediated silencing objective to verify gene function was not accomplished as anticipated. HSP70, a strong candidate protein that showed over-expression after TYLCV and SLCV acquisition and retention by B. tabaci, and co-localization with TYLCV in the midgut, was further studies. Besides this protein, our joint research resulted in the identification of many intriguing candidate genes and proteins that will be followed up by additional experiments during our future research. To identify these proteins it was necessary to increase the number and breadth of whitefly ESTs substantially and so whitefly cDNAs from various libraries made during the project were sequenced (Sanger, 454). As a result, the proteome annotation (ID) was far more successful than in the initial attempt to identify proteins using Uniprot or translated insect ESTs from public databases. The extent of homology shared by insects in different orders was surprisingly low, underscoring the imperative need for genome and transcriptome sequencing of homopteran insects. Having increased the number of EST from the original usable 5500 generated several years ago to >600,000 (this project+NCBI data mining), we have identified about one fifth of the whitefly proteome using these new resources. Also we have created a database that links all identified whitefly proteins to the PAVEdb-ESTs in the database, resulting in a useful dataset to which additional ESTS will be added. We are optimistic about the prospect of linking the proteome ID results to the transcriptome database to enable our own and other labs the opportunity to functionally annotate not only genes and proteins involved in our area of interest (whitefly mediated transmission) but for the plethora of other functionalities that will emerge from mining and functionally annotating other key genes and gene families in whitefly metabolism, development, among others. This joint grant has resulted in the identification of numerous candidate proteins involved in begomovirus transmission by B. tabaci. A next major step will be to capitalize on validated genes/proteins to develop approaches to interfere with the virus transmission.
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Orebaugh, Jack, i Pavlo Bohutskyi. Transcriptomic Network Analysis of Cyanobacterial-Methylotroph Interactions in Coculture and Axenic Conditions. Office of Scientific and Technical Information (OSTI), sierpień 2023. http://dx.doi.org/10.2172/1999433.
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