Articles de revues : « Transcriptomic response to N-starvation »

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Conesa, Carlos M., Angela Saez, Sara Navarro-Neila, Laura de Lorenzo, Arthur G. Hunt, Edgar B. Sepúlveda, Roberto Baigorri et al. « Alternative Polyadenylation and Salicylic Acid Modulate Root Responses to Low Nitrogen Availability ». Plants 9, n^o 2 (16 février 2020) : 251. http://dx.doi.org/10.3390/plants9020251.

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Nitrogen (N) is probably the most important macronutrient and its scarcity limits plant growth, development and fitness. N starvation response has been largely studied by transcriptomic analyses, but little is known about the role of alternative polyadenylation (APA) in such response. In this work, we show that N starvation modifies poly(A) usage in a large number of transcripts, some of them mediated by FIP1, a component of the polyadenylation machinery. Interestingly, the number of mRNAs isoforms with poly(A) tags located in protein-coding regions or 5′-UTRs significantly increases in response to N starvation. The set of genes affected by APA in response to N deficiency is enriched in N-metabolism, oxidation-reduction processes, response to stresses, and hormone responses, among others. A hormone profile analysis shows that the levels of salicylic acid (SA), a phytohormone that reduces nitrate accumulation and root growth, increase significantly upon N starvation. Meta-analyses of APA-affected and fip1-2-deregulated genes indicate a connection between the nitrogen starvation response and salicylic acid (SA) signaling. Genetic analyses show that SA may be important for preventing the overgrowth of the root system in low N environments. This work provides new insights on how plants interconnect different pathways, such as defense-related hormonal signaling and the regulation of genomic information by APA, to fine-tune the response to low N availability.

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Bedu, Magali, Anne Marmagne, Céline Masclaux-Daubresse et Fabien Chardon. « Transcriptional Plasticity of Autophagy-Related Genes Correlates with the Genetic Response to Nitrate Starvation in Arabidopsis Thaliana ». Cells 9, n^o 4 (20 avril 2020) : 1021. http://dx.doi.org/10.3390/cells9041021.

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In eukaryotes, autophagy, a catabolic mechanism for macromolecule and protein recycling, allows the maintenance of amino acid pools and nutrient remobilization. For a better understanding of the relationship between autophagy and nitrogen metabolism, we studied the transcriptional plasticity of autophagy genes (ATG) in nine Arabidopsis accessions grown under normal and nitrate starvation conditions. The status of the N metabolism in accessions was monitored by measuring the relative expression of 11 genes related to N metabolism in rosette leaves. The transcriptional variation of the genes coding for enzymes involved in ammonium assimilation characterize the genetic diversity of the response to nitrate starvation. Starvation enhanced the expression of most of the autophagy genes tested, suggesting a control of autophagy at transcriptomic level by nitrogen. The diversity of the gene responses among natural accessions revealed the genetic variation existing for autophagy independently of the nutritive condition, and the degree of response to nitrate starvation. We showed here that the genetic diversity of the expression of N metabolism genes correlates with that of the ATG genes in the two nutritive conditions, suggesting that the basal autophagy activity is part of the integral response of the N metabolism to nitrate availability.

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Lu, Li-Lan, Yu-Xiu Zhang et Yan-Fang Yang. « Integrative transcriptomic and metabolomic analyses unveil tanshinone biosynthesis in Salvia miltiorrhiza root under N starvation stress ». PLOS ONE 17, n^o 8 (25 août 2022) : e0273495. http://dx.doi.org/10.1371/journal.pone.0273495.

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Salvia miltiorrhiza is a model plant for Chinese herbal medicine with significant pharmacologic effects due to its tanshinone components. Our previous study indicated that nitrogen starvation stress increased its tanshinone content. However, the molecular mechanism of this low nitrogen-induced tanshinone biosynthesis is still unclear. Thus, this study aimed to elucidate the molecular mechanism of tanshinone biosynthesis in S. miltiorrhiza under different N conditions [N-free (N0), low-N (Nl), and full-N (Nf, as control) conditions] by using transcriptome and metabolome analyses. Our results showed 3,437 and 2,274 differentially expressed unigenes between N0 and Nf as well as Nl and Nf root samples, respectively. N starvation (N0 and Nl) promoted the expression of the genes involved in the MVA and MEP pathway of tanshinone and terpenoid backbone biosynthesis. Gene ontology and KEGG analyses revealed that terpenoid backbone biosynthesis, hormone signal transduction, and phenylpropanoid biosynthesis were promoted under N starvation conditions, whereas starch and sucrose metabolisms, nitrogen and phosphorus metabolisms, as well as membrane development were inhibited. Furthermore, metabolome analysis showed that metabolite compounds and biosynthesis of secondary metabolites were upregulated. This study provided a novel insight into the molecular mechanisms of tanshinone production in S. miltiorrhiza in response to nitrogen stress.

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Beszteri, Sára, Ines Yang, Nina Jaeckisch, Urban Tillmann, Stephan Frickenhaus, Gernot Glöckner, Allan Cembella et Uwe John. « Transcriptomic response of the toxic prymnesiophyte Prymnesium parvum (N. Carter) to phosphorus and nitrogen starvation ». Harmful Algae 18 (juin 2012) : 1–15. http://dx.doi.org/10.1016/j.hal.2012.03.003.

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Redon, Emma, Pascal Loubiere et Muriel Cocaign-Bousquet. « Transcriptome Analysis of the Progressive Adaptation of Lactococcus lactis to Carbon Starvation ». Journal of Bacteriology 187, n^o 10 (15 mai 2005) : 3589–92. http://dx.doi.org/10.1128/jb.187.10.3589-3592.2005.

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ABSTRACT Adaptation of Lactococcus lactis towards progressive carbon starvation is mediated by three different types of transcriptomic responses: (i) global responses, i.e., general decreases of functions linked to bacterial growth and lack of induction of the general stress response; (ii) specific responses functionally related to glucose exhaustion, i.e., underexpression of central metabolism genes, induction of alternative sugar transport and metabolism, and induction of the arginine deiminase pathway; and (iii) other responses never described previously during carbon starvation.

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Xiong, Rui, Hua Tang, Min Xu, Can-Bin Zeng, Yun Peng, Rui He, Zhen Yan, Zhao Qi et Yu Cheng. « Transcriptomic Analysis of Banana in Response to Phosphorus Starvation Stress ». Agronomy 8, n^o 8 (7 août 2018) : 141. http://dx.doi.org/10.3390/agronomy8080141.

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Bananas are an important part of the diets of millions of people around the globe. Low P absorption and use efficiency significantly restrict banana yields. To further explore the molecular mechanisms of P regulation in banana plants, we used RNA sequencing-based transcriptomic analysis for banana plants subjected to Pi deficit stress for 60 days. We detected 1900 significantly differentially expressed genes (DEGs) in aboveground plant parts and 7398 DEGs in root parts under low P stress. Gene ontology (GO) classification analysis showed that 156,291 GO terms belonging to molecular functions, 53,114 GO terms belonging to cellular components, and 228,544 GO terms belonging to biological processes were enriched in the aboveground and root components. A number of DEGs involved in energy metabolism-related processes, signal transduction, control of rhizosphere P activation, and Pi mobilization were found, which were confirmed by quantitative reverse-transcription Polymerase Chain Reaction (qRT-PCR) analysis. At the transcriptomic level, we detected 13 DEGs from different organs and with different functions in the time-course response to phosphorus deficiency stress. These DEGs may include some key genes that regulate the phosphorus network, increasing our understanding of the molecular mechanism of Pi homeostasis in banana. These findings will also help develop biotechnologies to create a variant of banana with more effective Pi absorption and utilization.

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Tralau, Tewes, Stéphane Vuilleumier, Christelle Thibault, Barry J. Campbell, C. Anthony Hart et Michael A. Kertesz. « Transcriptomic Analysis of the Sulfate Starvation Response of Pseudomonas aeruginosa ». Journal of Bacteriology 189, n^o 19 (3 août 2007) : 6743–50. http://dx.doi.org/10.1128/jb.00889-07.

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ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes a number of infections in humans, but is best known for its association with cystic fibrosis. It is able to use a wide range of sulfur compounds as sources of sulfur for growth. Gene expression in response to changes in sulfur supply was studied in P. aeruginosa E601, a cystic fibrosis isolate that displays mucin sulfatase activity, and in P. aeruginosa PAO1. A large family of genes was found to be upregulated by sulfate limitation in both isolates, encoding sulfatases and sulfonatases, transport systems, oxidative stress proteins, and a sulfate-regulated TonB/ExbBD complex. These genes were localized in five distinct islands on the genome and encoded proteins with a significantly reduced content of cysteine and methionine. Growth of P. aeruginosa E601 with mucin as the sulfur source led not only to a sulfate starvation response but also to induction of genes involved with type III secretion systems.

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Beleggia, Romina, Nooshin Omranian, Yan Holtz, Tania Gioia, Fabio Fiorani, Franca M. Nigro, Nicola Pecchioni et al. « Comparative Analysis Based on Transcriptomics and Metabolomics Data Reveal Differences between Emmer and Durum Wheat in Response to Nitrogen Starvation ». International Journal of Molecular Sciences 22, n^o 9 (30 avril 2021) : 4790. http://dx.doi.org/10.3390/ijms22094790.

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Mounting evidence indicates the key role of nitrogen (N) on diverse processes in plant, including development and defense. Using a combined transcriptomics and metabolomics approach, we studied the response of seedlings to N starvation of two different tetraploid wheat genotypes from the two main domesticated subspecies: emmer and durum wheat. We found that durum wheat exhibits broader and stronger response in comparison to emmer as seen from the expression pattern of both genes and metabolites and gene enrichment analysis. They showed major differences in the responses to N starvation for transcription factor families, emmer showed differential reduction in the levels of primary metabolites while durum wheat exhibited increased levels of most of them to N starvation. The correlation-based networks, including the differentially expressed genes and metabolites, revealed tighter regulation of metabolism in durum wheat in comparison to emmer. We also found that glutamate and γ-aminobutyric acid (GABA) had highest values of centrality in the metabolic correlation network, suggesting their critical role in the genotype-specific response to N starvation of emmer and durum wheat, respectively. Moreover, this finding indicates that there might be contrasting strategies associated to GABA and glutamate signaling modulating shoot vs. root growth in the two different wheat subspecies.

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Switzer, Amy, Daniel R. Brown et Sivaramesh Wigneshweraraj. « New insights into the adaptive transcriptional response to nitrogen starvation in Escherichia coli ». Biochemical Society Transactions 46, n^o 6 (4 décembre 2018) : 1721–28. http://dx.doi.org/10.1042/bst20180502.

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Bacterial adaptive responses to biotic and abiotic stresses often involve large-scale reprogramming of the transcriptome. Since nitrogen is an essential component of the bacterial cell, the transcriptional basis of the adaptive response to nitrogen starvation has been well studied. The adaptive response to N starvation in Escherichia coli is primarily a ‘scavenging response’, which results in the transcription of genes required for the transport and catabolism of nitrogenous compounds. However, recent genome-scale studies have begun to uncover and expand some of the intricate regulatory complexities that underpin the adaptive transcriptional response to nitrogen starvation in E. coli. The purpose of this review is to highlight some of these new developments.

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Su, Hui, Xueying Zhang, Yuqing He, Linying Li, Yuefei Wang, Gaojie Hong et Ping Xu. « Transcriptomic Analysis Reveals the Molecular Adaptation of Three Major Secondary Metabolic Pathways to Multiple Macronutrient Starvation in Tea (Camellia sinensis) ». Genes 11, n^o 3 (25 février 2020) : 241. http://dx.doi.org/10.3390/genes11030241.

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Tea (Camellia sinensis (L.) O. Kuntze) is a widely consumed beverage. Lack of macronutrients is a major cause of tea yield and quality losses. Though the effects of macronutrient starvation on tea metabolism have been studied, little is known about their molecular mechanisms. Hence, we investigated changes in the gene expression of tea plants under nitrogen (N), phosphate (P), and potassium (K) deficient conditions by RNA-sequencing. A total of 9103 differentially expressed genes (DEG) were identified. Function enrichment analysis showed that many biological processes and pathways were common to N, P, and K starvation. In particular, cis-element analysis of promoter of genes uncovered that members of the WRKY, MYB, bHLH, NF-Y, NAC, Trihelix, and GATA families were more likely to regulate genes involved in catechins, l-theanine, and caffeine biosynthetic pathways. Our results provide a comprehensive insight into the mechanisms of responses to N, P, and K starvation, and a global basis for the improvement of tea quality and molecular breeding.

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Tian, Jing, Yue Pang et Zhong Zhao. « Comparative Transcriptome Analysis of Sophora japonica (L.) Roots Reveals Key Pathways and Genes in Response to PEG-Induced Drought Stress under Different Nitrogen Conditions ». Forests 12, n^o 5 (20 mai 2021) : 650. http://dx.doi.org/10.3390/f12050650.

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Sophora japonica is a native leguminous tree species in China. The high stress tolerance contributes to its long lifespan of thousands of years. The lack of genomic resources greatly limits genetic studies on the stress responses of S. japonica. In this study, RNA-seq was conducted for S. japonica roots grown under short-term 20% polyethylene glycol (PEG) 6000-induced drought stress under normal N and N starvation conditions (1 and 0 mM NH4NO3, respectively). In each of the libraries, we generated more than 25 million clean reads, which were then de novo assembled to 46,852 unigenes with an average length of 1310.49 bp. In the differential expression analyses, more differentially expressed genes (DEGs) were found under drought with N starvation than under single stresses. The number of transcripts identified under N starvation and drought in S. japonica was nearly the same, but more upregulated genes were induced by drought, while more downregulated genes were induced by N starvation. Genes involved in “phenylpropanoid biosynthesis” and “biosynthesis of amino acids” pathways were upregulated according to KEGG enrichment analyses, irrespective of the stress treatments. Additionally, upregulated N metabolism genes were enriched upon drought, and downregulated photosynthesis genes were enriched under N starvation. We found 4,372 and 5,430 drought-responsive DEGs under normal N and N starvation conditions, respectively. N starvation may aggravate drought by downregulating transcripts in the “carbon metabolism”, “ribosome”, “arginine biosynthesis pathway”, “oxidative phosphorylation” and “aminoacyl-tRNA biosynthesis” pathways. We identified 78 genes related to N uptake and assimilation, 38 of which exhibited differential expression under stress. A total of 395 DEGs were categorized as transcription factors, of which AR2/ERF-ERF, WRKY, NAC, MYB, bHLH, C3H and C2C2-Dof families played key roles in drought and N starvation stresses. The transcriptome data obtained, and the genes identified facilitate our understanding of the mechanisms of S. japonica responses to drought and N starvation stresses and provide a molecular foundation for understanding the mechanisms of its long lifespan for breeding resistant varieties for greening.

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Kokina, Agnese, Kristel Tanilas, Zane Ozolina, Karlis Pleiko, Karlis Shvirksts, Ilze Vamza et Janis Liepins. « Purine Auxotrophic Starvation Evokes Phenotype Similar to Stationary Phase Cells in Budding Yeast ». Journal of Fungi 8, n^o 1 (29 décembre 2021) : 29. http://dx.doi.org/10.3390/jof8010029.

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Purine auxotrophy is an abundant trait among eukaryotic parasites and a typical marker for many budding yeast strains. Supplementation with an additional purine source (such as adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We explored purine starvation effects in a model organism, a budding yeast Saccharomyces cerevisiae ade8 knockout, at the level of cellular morphology, central carbon metabolism, and global transcriptome. We observed that purine-starved cells stopped their cycle in G1/G0 state and accumulated trehalose, and the intracellular concentration of AXP decreased, but adenylate charge remained stable. Cells became tolerant to severe environmental stresses. Intracellular RNA concentration decreased, and massive downregulation of ribosomal biosynthesis genes occurred. We proved that the expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype Msn2/4p targets are upregulated in purine-starved cells when compared to cells cultivated in purine-rich media. The overall transcriptomic response to purine starvation resembles that of stationary phase cells. Our results demonstrate that the induction of a strong stress resistance phenotype in budding yeast can be caused not only by natural starvation, but also starvation for metabolic intermediates, such as purines.

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Lim, Li, et Abdul Hafiz Ab Majid. « Analysis of Transcriptome Difference between Blood-Fed and Starved Tropical Bed Bug, Cimex hemipterus (F.) (Hemiptera : Cimicidae) ». Insects 13, n^o 4 (14 avril 2022) : 387. http://dx.doi.org/10.3390/insects13040387.

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The reference transcriptome for Cimex hemipterus (tropical bed bug) was assembled de novo in this study, and differential expression analysis was conducted between blood-fed and starved tropical bed bug. A total of 24,609 transcripts were assembled, with around 79% of them being annotated against the Eukaryotic Orthologous Groups (KOG) database. The transcriptomic comparison revealed several differentially expressed genes between blood-fed and starved bed bugs, with 38 of them being identifiable. There were 20 and 18 genes significantly upregulated in blood-fed and starved bed bugs, respectively. Differentially expressed genes (DEGs) were revealed to be associated with regulation, metabolism, transport, motility, immune, and stress response; endocytosis; and signal transduction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed an enrichment of genes encoding steroid biosynthesis, glycosaminoglycan biosynthesis, butanoate metabolism, and autophagy in both blood-fed and starved bed bugs. However, in blood-fed bed bugs, genes involved in histidine metabolism, caffeine metabolism, ubiquinone/terpenoid-quinone biosynthesis, and sulfur relay system were enriched. On the other hand, starvation activates genes related to nicotinate and nicotinamide metabolism, fatty acid elongation, terpenoid backbone biosynthesis, metabolism of xenobiotics by cytochrome P450, riboflavin metabolism, apoptosis, and protein export. The present study is the first to report a de novo transcriptomic analysis in C. hemipterus and demonstrated differential responses of bed bugs in facing blood-feeding and starvation.

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Wu, Zhihua, Hong Liu, Wen Huang, Lisha Yi, Erdai Qin, Tiange Yang, Jing Wang et Rui Qin. « Genome-Wide Identification, Characterization, and Regulation of RWP-RK Gene Family in the Nitrogen-Fixing Clade ». Plants 9, n^o 9 (11 septembre 2020) : 1178. http://dx.doi.org/10.3390/plants9091178.

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RWP-RK is a plant-specific family of transcription factors, involved in nitrate response, gametogenesis, and nodulation. However, genome-wide characterization, phylogeny, and the regulation of RWP-RK genes in the nodulating and non-nodulating plant species of nitrogen-fixing clade (NFC) are widely unknown. Therefore, we identified a total of 292 RWP-RKs, including 278 RWP-RKs from 25 NFC species and 14 RWP-RKs from the outgroup, Arabidopsis thaliana. We classified the 292 RWP-RKs in two subfamilies: the NIN-like proteins (NLPs) and the RWP-RK domain proteins (RKDs). The transcriptome and phylogenetic analysis of RWP-RKs suggested that, compared to RKD genes, the NLP genes were just upregulated in nitrate response and nodulation. Moreover, nodule-specific NLP genes of some nodulating NFC species may have a common ancestor (OG0002084) with AtNLP genes in A. thaliana. Further, co-expression networks of A.thaliana under N-starvation and N-supplementation conditions revealed that there is a higher correlation between expression of AtNLP genes and symbiotic genes during N-starvation. In P. vulgaris, we confirmed that N-starvation stimulated nodulation by regulating expression of PvNLP2, closely related to AtNLP6 and AtNLP7 with another common origin (OG0004041). Taken together, we concluded that different origins of the NLP genes involved in both N-starvation response and specific expression of nodulation would contribute to the evolution of nodulation in NFC plant species. Our results shed light on the phylogenetic relationships of NLP genes and their differential regulation in nitrate response of A. thaliana and nodulation of NFC.

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Zulfiqar, Alveena, Beenish Jehan Azhar, Aroosa Zeb, Asyia Zeenat, Sitwat Aman, Scott A. Heckerthorn et Samina N. Shakeel. « Screening of Rice Varieties based on Remodeling of Root Architecture Linked to Enhanced Phosphorus Transporters and Ethylene Signaling for Better Phosphorous Acquisition under Limiting Conditions ». Sains Malaysiana 50, n^o 6 (30 juin 2021) : 1621–38. http://dx.doi.org/10.17576/jsm-2021-5006-10.

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Root architectural modifications in response to altered nutrient level can be used as selection marker for better adapted rice varieties. In this study, we screened six local rice varieties commonly grown in Pakistan, using their unique root architecture and several molecular markers to identify best adapted local variety under phosphorus limiting conditions. Our data showed that rice variety with significant changes in its three-dimensional root architecture system (RSA) and enhanced expression of phosphorus transporters (OsPT2, OsPT4 and OsPT6) is the best variety to handle stress as compared to other varieties. Along with development of screening strategy/method, our data provided evidence that phosphorus starvation leads to upregulation of stress hormone ethylene, which regulates root elongation and root hair development therefore facilitating root architecture modification. We then further checked, how to mitigate or enhance phosphorus starvation responses by application of hormones exogenously, our results showed that ethylene application/treatment enhances phosphorus starvation responses, whereas cytokinin on the other hand reverses deficiency effects which implicates hormonal cross talk is key to modulate P-deficiency responses in rice. This study provides an easy and quick method of analysis of root architecture as physiological marker for rice screening and improve crop yield by selecting best adapted variety for P deficient soils. In future, detail study for understanding phytohormone mediated transcriptomic changes in response to nutrient deficiency and in correlation with physiological response will help to select better adapted varieties that will eventually result in increase of rice yield.

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Kaur, Gazaldeep, Vishnu Shukla, Anil Kumar, Mandeep Kaur, Parul Goel, Palvinder Singh, Anuj Shukla et al. « Integrative analysis of hexaploid wheat roots identifies signature components during iron starvation ». Journal of Experimental Botany 70, n^o 21 (7 septembre 2019) : 6141–61. http://dx.doi.org/10.1093/jxb/erz358.

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Abstract Iron (Fe) is an essential micronutrient for all organisms. In crop plants, Fe deficiency can decrease crop yield significantly; however, our current understanding of how major crops respond to Fe deficiency remains limited. Herein, the effect of Fe deprivation at both the transcriptomic and metabolic level in hexaploid wheat was investigated. Genome-wide gene expression reprogramming was observed in wheat roots subjected to Fe starvation, with a total of 5854 genes differentially expressed. Homoeologue and subgenome-specific analysis unveiled the induction-biased contribution from the A and B genomes. In general, the predominance of genes coding for nicotianamine synthase, yellow stripe-like transporters, metal transporters, ABC transporters, and zinc-induced facilitator-like protein was noted. Expression of genes related to the Strategy II mode of Fe uptake was also predominant. Our transcriptomic data were in agreement with the GC-MS analysis that showed the enhanced accumulation of various metabolites such as fumarate, malonate, succinate, and xylofuranose, which could be contributing to Fe mobilization. Interestingly, Fe starvation leads to a significant temporal increase of glutathione S-transferase at both the transcriptional level and enzymatic activity level, which indicates the involvement of glutathione in response to Fe stress in wheat roots. Taken together, our result provides new insight into the wheat response to Fe starvation at the molecular level and lays the foundation to design new strategies for the improvement of Fe nutrition in crops.

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Mendes-Ferreira, A., M. del Olmo, J. García-Martínez, E. Jiménez-Martí, A. Mendes-Faia, J. E. Pérez-Ortín et C. Leão. « Transcriptional Response of Saccharomyces cerevisiae to Different Nitrogen Concentrations during Alcoholic Fermentation ». Applied and Environmental Microbiology 73, n^o 9 (2 mars 2007) : 3049–60. http://dx.doi.org/10.1128/aem.02754-06.

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ABSTRACT Gene expression profiles of a wine strain of Saccharomyces cerevisiae PYCC4072 were monitored during alcoholic fermentations with three different nitrogen supplies: (i) control fermentation (with enough nitrogen to complete sugar fermentation), (ii) nitrogen-limiting fermentation, and (iii) the addition of nitrogen to the nitrogen-limiting fermentation (refed fermentation). Approximately 70% of the yeast transcriptome was altered in at least one of the fermentation stages studied, revealing the continuous adjustment of yeast cells to stressful conditions. Nitrogen concentration had a decisive effect on gene expression during fermentation. The largest changes in transcription profiles were observed when the early time points of the N-limiting and control fermentations were compared. Despite the high levels of glucose present in the media, the early responses of yeast cells to low nitrogen were characterized by the induction of genes involved in oxidative glucose metabolism, including a significant number of mitochondrial associated genes resembling the yeast cell response to glucose starvation. As the N-limiting fermentation progressed, a general downregulation of genes associated with catabolism was observed. Surprisingly, genes encoding ribosomal proteins and involved in ribosome biogenesis showed a slight increase during N starvation; besides, genes that comprise the RiBi regulon behaved distinctively under the different experimental conditions. Here, for the first time, the global response of nitrogen-depleted cells to nitrogen addition under enological conditions is described. An important gene expression reprogramming occurred after nitrogen addition; this reprogramming affected genes involved in glycolysis, thiamine metabolism, and energy pathways, which enabled the yeast strain to overcome the previous nitrogen starvation stress and restart alcoholic fermentation.

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Farjad, Mahsa, Martine Rigault, Stéphanie Pateyron, Marie-Laure Martin-Magniette, Anne Krapp, Christian Meyer et Mathilde Fagard. « Nitrogen Limitation Alters the Response of Specific Genes to Biotic Stress ». International Journal of Molecular Sciences 19, n^o 11 (27 octobre 2018) : 3364. http://dx.doi.org/10.3390/ijms19113364.

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In their natural environment, plants are generally confronted with multiple co-occurring stresses. However, the interaction between stresses is not well known and transcriptomic data in response to combined stresses remain scarce. This study aims at characterizing the interaction between transcriptomic responses to biotic stress and nitrogen (N) limitation. Plants were grown in low or full N, infected or not with Erwinia amylovora (Ea) and plant gene expression was analyzed through microarray and qRT-PCR. Most Ea-responsive genes had the same profile (induced/repressed) in response to Ea in low and full N. In response to stress combination, one third of modulated transcripts responded in a manner that could not be deduced from their response to each individual stress. Many defense-related genes showed a prioritization of their response to biotic stress over their response to N limitation, which was also observed using Pseudomonas syringae as a second pathosystem. Our results indicate an interaction between transcriptomic responses to N and biotic stress. A small fraction of transcripts was prioritized between antagonistic responses, reflecting a preservation of the plant defense program under N limitation. Furthermore, this interaction also led to a complex and specific response in terms of metabolism and cellular homeostasis-associated genes.

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Chen, Xiangning, Yili Xu, Xiangyu Cui, Siying Zhang, Xiangqi Zhong, Juntao Ke, Yuze Wu et al. « Starvation Affects the Muscular Morphology, Antioxidant Enzyme Activity, Expression of Lipid Metabolism-Related Genes, and Transcriptomic Profile of Javelin Goby (Synechogobius hasta) ». Aquaculture Nutrition 2022 (30 décembre 2022) : 1–20. http://dx.doi.org/10.1155/2022/7057571.

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Fish in natural and cultivated environments can be challenged by starvation. However, inducing starvation in a controlled manner cannot only reduce feed consumption but also reduces aquatic eutrophication and even improves farmed fish quality. This study investigated the effects of starvation on the muscular function, morphology, and regulatory signaling in javelin goby (Synechogobius hasta) by evaluating the biochemical, histological, antioxidant, and transcriptional changes in the musculature of S. hasta subjected to 3, 7, and 14 days fasting. The muscle glycogen and triglyceride levels in S. hasta were gradually reduced under starvation, reaching their lowest at the end of the trial ( P < 0.05 ). The levels of glutathione and superoxide dismutase were significantly elevated after 3–7 days of starvation ( P < 0.05 ), but later returned to the level of the control group. The muscle of starved S. hasta developed structural abnormalities in some areas after 7 days of food deprivation, and more vacuolation and more atrophic myofibers were observed in 14-day fasted fish. The transcript levels of stearoyl-CoA desaturase 1 (scd1), the key gene involved in the biosynthesis of monounsaturated fatty acids, were markedly lower in the groups starved for 7 or more days ( P < 0.05 ). However, the relative expressions of genes associated with lipolysis were decreased in the fasting experiment ( P < 0 .05). Similar declines in the transcriptional response to starvation were found in muscle fatp1 and ppar γ abundance ( P < 0.05 ). Furthermore, the de novo transcriptome of muscle tissue from the control, 3-day and 14-day starved S. hasta generated 79,255 unigenes. The numbers of differentially expressed genes (DEGs) identified by pairwise comparisons among three groups were 3276, 7354, and 542, respectively. The enrichment analysis revealed that the DEGs were primarily involved in metabolism-related pathways, including ribosome, TCA pathway, and pyruvate metabolism. Moreover, the qRT-PCR results of 12 DEGs validated the expression trends observed in the RNA-seq data. Taken together, these findings demonstrated the specific phenotypical and molecular responses of muscular function and morphology in starved S. hasta, which may offer preliminary reference data for optimizing operational strategies incorporating fasting/refeeding cycles in aquaculture.

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Mascia, Maria, Davide Sega, Anita Zamboni et Zeno Varanini. « Nitrogen Starvation Differentially Influences Transcriptional and Uptake Rate Profiles in Roots of Two Maize Inbred Lines with Different NUE ». International Journal of Molecular Sciences 20, n^o 19 (30 septembre 2019) : 4856. http://dx.doi.org/10.3390/ijms20194856.

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Nitrogen use efficiency (NUE) of crops is estimated to be less than 50%, with a strong impact on environment and economy. Genotype-dependent ability to cope with N shortage has been only partially explored in maize and, in this context, the comparison of molecular responses of lines with different NUE is of particular interest in order to dissect the key elements underlying NUE. Changes in root transcriptome and NH4+/NO3− uptake rates during growth (after 1 and 4 days) without N were studied in high (Lo5) and low (T250) NUE maize inbred lines. Results suggests that only a small set of transcripts were commonly modulated in both lines in response to N starvation. However, in both lines, transcripts linked to anthocyanin biosynthesis and lateral root formation were positively affected. On the contrary, those involved in root elongation were downregulated. The main differences between the two lines reside in the ability to modulate the transcripts involved in the transport, distribution and assimilation of mineral nutrients. With regard to N mineral forms, only the Lo5 line responded to N starvation by increasing the NH4+ fluxes as supported by the upregulation of a transcript putatively involved in its transport.

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Gardeux, Vincent, Joanne Berghout, Ikbel Achour, A. Grant Schissler, Qike Li, Colleen Kenost, Jianrong Li et al. « A genome-by-environment interaction classifier for precision medicine : personal transcriptome response to rhinovirus identifies children prone to asthma exacerbations ». Journal of the American Medical Informatics Association 24, n^o 6 (22 juillet 2017) : 1116–26. http://dx.doi.org/10.1093/jamia/ocx069.

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Abstract Objective To introduce a disease prognosis framework enabled by a robust classification scheme derived from patient-specific transcriptomic response to stimulation. Materials and Methods Within an illustrative case study to predict asthma exacerbation, we designed a stimulation assay that reveals individualized transcriptomic response to human rhinovirus. Gene expression from peripheral blood mononuclear cells was quantified from 23 pediatric asthmatic patients and stimulated in vitro with human rhinovirus. Responses were obtained via the single-subject gene set testing methodology “N-of-1-pathways.” The classifier was trained on a related independent training dataset (n = 19). Novel visualizations of personal transcriptomic responses are provided. Results Of the 23 pediatric asthmatic patients, 12 experienced recurrent exacerbations. Our classifier, using individualized responses and trained on an independent dataset, obtained 74% accuracy (area under the receiver operating curve of 71%; 2-sided P = .039). Conventional classifiers using messenger RNA (mRNA) expression within the viral-exposed samples were unsuccessful (all patients predicted to have recurrent exacerbations; accuracy of 52%). Discussion Prognosis based on single time point, static mRNA expression alone neglects the importance of dynamic genome-by-environment interplay in phenotypic presentation. Individualized transcriptomic response quantified at the pathway (gene sets) level reveals interpretable signals related to clinical outcomes. Conclusion The proposed framework provides an innovative approach to precision medicine. We show that quantifying personal pathway–level transcriptomic response to a disease-relevant environmental challenge predicts disease progression. This genome-by-environment interaction assay offers a noninvasive opportunity to translate omics data to clinical practice by improving the ability to predict disease exacerbation and increasing the potential to produce more effective treatment decisions.

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Yim, Jaewoo, Sung Won Cho, Beomhee Kim, Sungwoo Park, Yong Hee Han et Sang Woo Seo. « Transcriptional Profiling of the Probiotic Escherichia coli Nissle 1917 Strain under Simulated Microgravity ». International Journal of Molecular Sciences 21, n^o 8 (11 avril 2020) : 2666. http://dx.doi.org/10.3390/ijms21082666.

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Long-term space missions affect the gut microbiome of astronauts, especially the viability of some pathogens. Probiotics may be an effective solution for the management of gut microbiomes, but there is a lack of studies regarding the physiology of probiotics in microgravity. Here, we investigated the effects of microgravity on the probiotic Escherichia coli Nissle 1917 (EcN) by comparing transcriptomic data during exponential and stationary growth phases under simulated microgravity and normal gravity. Microgravity conditions affected several physiological features of EcN, including its growth profile, biofilm formation, stress responses, metal ion transport/utilization, and response to carbon starvation. We found that some changes, such as decreased adhesion ability and acid resistance, may be disadvantageous to EcN relative to gut pathogens under microgravity, indicating the need to develop probiotics optimized for space flight.

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da Matta, Vania Lucia R., André N. Gonçalves, Cláudia Maria C. Gomes, Islam H. Chouman, Frederico M. Ferreira, Marliane B. Campos, Luciana V. Lima et al. « Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil ». Microorganisms 11, n^o 3 (3 mars 2023) : 653. http://dx.doi.org/10.3390/microorganisms11030653.

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Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical–immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.

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López, Cristina María, Manuel Pineda et Josefa M. Alamillo. « Transcriptomic Response to Water Deficit Reveals a Crucial Role of Phosphate Acquisition in a Drought-Tolerant Common Bean Landrace ». Plants 9, n^o 4 (2 avril 2020) : 445. http://dx.doi.org/10.3390/plants9040445.

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Drought is one of the most critical factors limiting legume crop productivity. Understanding the molecular mechanisms of drought tolerance in the common bean is required to improve the yields of this important crop under adverse conditions. In this work, RNA-seq analysis was performed to compare the transcriptome profiles of drought-stressed and well-irrigated plants of a previously characterized drought-tolerant common bean landrace. The analysis revealed responses related with the abscisic acid signaling, including downregulation of a phosphatase 2C (PP2C) and an abscisic acid-8′ hydroxylase, and upregulation of several key transcription factors and genes involved in cell wall remodeling, synthesis of osmoprotectants, protection of photosynthetic apparatus, and downregulation of genes involved in cell expansion. The results also highlighted a significant proportion of differentially expressed genes related to phosphate starvation response. In addition, the moderate detrimental effects of drought in the biomass of these tolerant plants were abolished by the addition of phosphate, thus indicating that, besides the ABA-mediated response, acquisition of phosphate could be crucial for the drought tolerance of this common bean genotype. These results provided information about the mechanisms involved in drought response of common bean response that could be useful for enhancing the drought tolerance of this important crop legume.

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Williamson, Kerry S., Mensur Dlakić, Tatsuya Akiyama et Michael J. Franklin. « The Pseudomonas aeruginosa RpoH (σ32) Regulon and Its Role in Essential Cellular Functions, Starvation Survival, and Antibiotic Tolerance ». International Journal of Molecular Sciences 24, n^o 2 (12 janvier 2023) : 1513. http://dx.doi.org/10.3390/ijms24021513.

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The bacterial heat-shock response is regulated by the alternative sigma factor, σ32 (RpoH), which responds to misfolded protein stress and directs the RNA polymerase to the promoters for genes required for protein refolding or degradation. In P. aeruginosa, RpoH is essential for viability under laboratory growth conditions. Here, we used a transcriptomics approach to identify the genes of the RpoH regulon, including RpoH-regulated genes that are essential for P. aeruginosa. We placed the rpoH gene under control of the arabinose-inducible PBAD promoter, then deleted the chromosomal rpoH allele. This allowed transcriptomic analysis of the RpoH (σ32) regulon following a short up-shift in the cellular concentration of RpoH by arabinose addition, in the absence of a sudden change in temperature. The P. aeruginosa ∆rpoH (PBAD-rpoH) strain grew in the absence of arabinose, indicating that some rpoH expression occurred without arabinose induction. When arabinose was added, the rpoH mRNA abundance of P. aeruginosa ∆rpoH (PBAD-rpoH) measured by RT-qPCR increased five-fold within 15 min of arabinose addition. Transcriptome results showed that P. aeruginosa genes required for protein repair or degradation are induced by increased RpoH levels, and that many genes essential for P. aeruginosa growth are induced by RpoH. Other stress response genes induced by RpoH are involved in damaged nucleic acid repair and in amino acid metabolism. Annotation of the hypothetical proteins under RpoH control included proteins that may play a role in antibiotic resistances and in non-ribosomal peptide synthesis. Phenotypic analysis of P. aeruginosa ∆rpoH (PBAD-rpoH) showed that it is impaired in its ability to survive during starvation compared to the wild-type strain. P. aeruginosa ∆rpoH (PBAD-rpoH) also had increased sensitivity to aminoglycoside antibiotics, but not to other classes of antibiotics, whether cultured planktonically or in biofilms. The enhanced aminoglycoside sensitivity of the mutant strain may be due to indirect effects, such as the build-up of toxic misfolded proteins, or to the direct effect of genes, such as aminoglycoside acetyl transferases, that are regulated by RpoH. Overall, the results demonstrate that RpoH regulates genes that are essential for viability of P. aeruginosa, that it protects P. aeruginosa from damage from aminoglycoside antibiotics, and that it is required for survival during nutrient-limiting conditions.

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Palstra, Arjan P., Diego Crespo, Guido E. E. J. M. van den Thillart et Josep V. Planas. « Saving energy to fuel exercise : swimming suppresses oocyte development and downregulates ovarian transcriptomic response of rainbow trout Oncorhynchus mykiss ». American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 299, n^o 2 (août 2010) : R486—R499. http://dx.doi.org/10.1152/ajpregu.00109.2010.

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Metabolic processes and sexual maturation closely interact during the long-distance reproductive migration of many fish species to their spawning grounds. In the present study, we have used exercise experimentally to investigate the effects on sexual maturation in rainbow trout. Pubertal autumn-spawning seawater-raised female rainbow trout Oncorhynchus mykiss ( n = 26; 50 cm, 1.5 kg) were rested or swum at a near optimal speed of 0.75 body lengths per second in a 6,000-liter swim flume under natural reproductive conditions (16°C fresh-water, starvation, 8:16-h light-dark photoperiod). Fish were sampled after arrival and subsequently after 10 days (resting or swimming 307 km) and 20 days (resting or swimming 636 km). Ovarian development was significantly reduced in the swimmers. Analysis of the expression of key factors in the reproductive axis included pituitary kiss1-receptor, lh, and fsh and ovarian lh-receptor, fsh-receptor, aromatase, and vitellogenin-receptor ( vtgr). Swimmers had lower pituitary lh and ovarian vtgr expression than resters. Furthermore, the number of late vitellogenic oocytes was lower in swimmers than in resters, probably resulting from the lower vtgr expression, and vitellogenin plasma levels were higher. Therefore, swimming exercise suppresses oocyte development possibly by inhibiting vitellogenin uptake. Transcriptomic changes that occurred in the ovary of exercised fish were investigated using a salmonid cDNA microarray platform. Protein biosynthesis and energy provision were among the 16 functional categories that were all downregulated in the ovary. Downregulation of the transcriptomic response in the ovary illustrates the priority of energy reallocation and will save energy to fuel exercise. A swimming-induced ovarian developmental suppression at the start of vitellogenesis during long-term reproductive migration may be a strategy to avoid precocious muscle atrophy.

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Hases, Linnea, Madeleine Birgersson, Rajitha Indukuri, Amena Archer et Cecilia Williams. « Colitis Induces Sex-Specific Intestinal Transcriptomic Responses in Mice ». International Journal of Molecular Sciences 23, n^o 18 (8 septembre 2022) : 10408. http://dx.doi.org/10.3390/ijms231810408.

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There are significant sex differences in colorectal cancer (CRC), including in incidence, onset, and molecular characteristics. Further, while inflammatory bowel disease (IBD) is a risk factor for CRC in both sexes, men with IBD have a 60% higher risk of developing CRC compared to women. In this study, we investigated sex differences during colitis-associated CRC (CAC) using a chemically induced CAC mouse model. The mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) and followed for 9 and 15 weeks. We performed RNA-sequencing of colon samples from males (n = 15) and females (n = 15) to study different stages of inflammation and identify corresponding transcriptomic sex differences in non-tumor colon tissue. We found a significant transcriptome response to AOM/DSS treatment in both sexes, including in pathways related to inflammation and cell proliferation. Notably, we found a stronger response in males and that male-specific differentially expressed genes were involved in NFκB signaling and circadian rhythm. Further, an overrepresented proportion of male-specific gene regulations were predicted to be targets of Stat3, whereas for females, targets of the glucocorticoid receptor (Gr/Nr3c1) were overrepresented. At 15 weeks, the most apparent sex difference involved genes with functions in T cell proliferation, followed by the regulation of demethylases. The majority of sex differences were thus related to inflammation and the immune system. Our novel data, profiling the transcriptomic response to chemically induced colitis and CAC, indicate clear sex differences in CRC initiation and progression.

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Wei, Li, Wuxin You, Zhengru Xu et Wenfei Zhang. « Transcriptomic survey reveals multiple adaptation mechanisms in response to nitrogen deprivation in marine Porphyridium cruentum ». PLOS ONE 16, n^o 11 (18 novembre 2021) : e0259833. http://dx.doi.org/10.1371/journal.pone.0259833.

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Single-cell red microalga Porphyridium cruentum is potentially considered to be the bioresource for biofuel and pharmaceutical production. Nitrogen is a kind of nutrient component for photosynthetic P. cruentum. Meanwhile, nitrogen stress could induce to accumulate some substances such as lipid and phycoerythrin and affect its growth and physiology. However, how marine microalga Porphyridium cruentum respond and adapt to nitrogen starvation remains elusive. Here, acclimation of the metabolic reprogramming to changes in the nutrient environment was studied by high-throughput mRNA sequencing in the unicellular red alga P. cruentum. Firstly, to reveal transcriptional regulation, de novo transcriptome was assembled and 8,244 unigenes were annotated based on different database. Secondly, under nitrogen deprivation, 2100 unigenes displayed differential expression (1134 upregulation and 966 downregulation, respectively) and some pathways including carbon/nitrogen metabolism, photosynthesis, and lipid metabolism would be reprogrammed in P. cruentum. The result demonstrated that nitrate assimilation (with related unigenes of 8–493 fold upregulation) would be strengthen and photosynthesis (with related unigenes of 6–35 fold downregulation) be impaired under nitrogen deprivation. Importantly, compared to other green algae, red microalga P. cruentum presented a different expression pattern of lipid metabolism in response to nitrogen stress. These observations will also provide novel insight for understanding adaption mechanisms and potential targets for metabolic engineering and synthetic biology in P. cruentum.

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Liu, David, Bastian Schilling, Derek Liu, Antje Sucker, Elisabeth Livingstone, Livnat Jerby-Arnon, Lisa Zimmer et al. « Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma ». Nature Medicine 25, n^o 12 (décembre 2019) : 1916–27. http://dx.doi.org/10.1038/s41591-019-0654-5.

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AbstractImmune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors of response compared to tumors that were naive to ICB, suggesting selective immune effects of previous exposure to anti-CTLA4 ICB. Finally, we developed parsimonious models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 ICB in individual tumors, with validation in smaller independent cohorts limited by the availability of comprehensive data. Broadly, we present a framework to discover predictive features and build models of ICB therapeutic response.

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Yan, Lei, Liang Su, Rui Li, Hao Li, Jianrong Bai et Fengjie Sun. « Differential Gene Expression Responding to Low Phosphate Stress in Leaves and Roots of Maize by cDNA-SRAP ». BioMed Research International 2020 (21 juillet 2020) : 1–13. http://dx.doi.org/10.1155/2020/8420151.

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Phosphate (Pi) deficiency in soil can have severe impacts on the growth, development, and production of maize worldwide. In this study, a cDNA-sequence-related amplified polymorphism (cDNA-SRAP) transcript profiling technique was used to evaluate the gene expression in leaves and roots of maize under Pi stress for seven days. A total of 2494 differentially expressed fragments (DEFs) were identified in response to Pi starvation with 1202 and 1292 DEFs in leaves and roots, respectively, using a total of 60 primer pairs in the cDNA-SRAP analysis. These DEFs were categorized into 13 differential gene expression patterns. Results of sequencing and functional analysis showed that 63 DEFs (33 in leaves and 30 in roots) were annotated to a total of 54 genes involved in diverse groups of biological pathways, including metabolism, photosynthesis, signal transduction, transcription, transport, cellular processes, genetic information, and organismal system. This study demonstrated that (1) the cDNA-SRAP transcriptomic profiling technique is a powerful method to analyze differential gene expression in maize showing advantageous features among several transcriptomic methods; (2) maize undergoes a complex adaptive process in response to low Pi stress; and (3) a total of seven differentially expressed genes were identified in response to low Pi stress in leaves or roots of maize and could be used in the genetic modification of maize.

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FRENEL, Jean Sebastien, Fadoua Ben Azzouz, Frederic Bigot, Jonathan Dauve, Marie Francoise Heymann, Wilfried Gouraud, Catherine Guette et al. « Abstract P5-02-37 : Multi-omics approach to identify markers of resistance to endocrine therapy + CDK4/6 inhibitors in first line HR+/HER2- metastatic breast cancer (MBC) patients ». Cancer Research 83, n^o 5_Supplement (1 mars 2023) : P5–02–37—P5–02–37. http://dx.doi.org/10.1158/1538-7445.sabcs22-p5-02-37.

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Abstract CONTEXT: Endocrine therapy combined with CDK4/6 inhibitor is the standard frontline treatment for the vast majority of HR+/HER2- MBC patients. Despite an overall survival benefit, patients eventually progress and mechanisms of resistance to this combination are not well identified. METHODS: EPICURE is an ongoing pilot prospective cohort study of heterogeneous and massive data integration, ie. multi-omics approach in MBC patients. The present study aims at identifying progression markers in patients with HR+/HER2- MBC receiving frontline endocrine therapy+iCDK4/6 by means of transcriptomics, genomics and proteomics data. All patients had a tumor biopsy at the entry in the study (B1) and a biopsy was repeated at progression if feasible (B2). Transcriptomic (RNAseq: NextSeq550, Illumina), genomic (whole exome sequencing: NextSeq550, Illumina) and proteomic (DIA mass spectrometry: TimsTOFPro2, Bruker) were performed on B1 and B2 according to available tumor tissue. RESULTS: Fifty-one patients matching inclusion criteria were included. B1 was done at inclusion for all patients (B1) (n = 51) and B2 was performed in 8 patients. (B2) (n = 8). Eight metastatic sites were biopsied: node (n = 17); liver (n = 16); bone (n = 8); breast local recurrence (n = 5); chest wall (n = 5); skin (n = 4); pleural (n = 3); ovary (n = 1). Transcriptomic, genomic and proteomic analysis of paired biopsies (B1 and B2) was performed in parallel and separately for 8, 7 and 2 patients, respectively. Exploratory data analysis of transcriptomic and proteomic data showed that liver biopsies clustered together. In order to eliminate this anatomic bias, specific genes and proteins of liver metastases were identified by means of DESeq2 analysis (12 liver vs 39 other sites) for transcriptomic data (n = 2654) and LIMMA (4 liver vs 14 other sites) for proteomic data (n = 227), and excluded for the rest of the analysis. Differential analyses (ie. gene expression, non-synonymous mutations and protein expression) between B1 and B2 were performed for each patient. These three kind of lists were finally submitted to ToppGene, DAVID and GOrilla for Gene Ontology terms enrichment analyses. Transcriptomic analyses of the 8 paired biopsies highlighted immune response (IR) in seven B1, IR in four B2 and neurogenesis in three B2. Genomics data evaluation between B1 and B2 pointed out “transposon integration” as an important pathway. Proteomic data of the 2 paired biopsies analysed underlined high immune response in B1, and muscle development/contraction and response to tumor necrosis factor in B2 for one patient. For the second one, liver metabolism in B1 and extracellular matrix and p38 MAPK cascade were emphasised. CONCLUSION: This preliminary study based on transcriptomic, genomic and proteomic data represents an encouraging first step of the EPICURE project. In a near future, additional paired biopsies and other kinds of omics data (epigenetics, radiomics, microbiomics, exposomics) will be available. Furthermore, omics data will be analysed in an integrated manner (ie. artificial intelligence), which will make it possible to detect synergies across the different omics data. Citation Format: Jean Sebastien FRENEL, Fadoua Ben Azzouz, Frederic Bigot, Jonathan Dauve, Marie Francoise Heymann, Wilfried Gouraud, Catherine Guette, Hamza Lasla, Bertrand Michel, Alain Morel, Anne Patsouris, Marie Robert, Grégoire Siekaniec, Mathilde Colombie, Pascal Jézéquel, Mario Campone. Multi-omics approach to identify markers of resistance to endocrine therapy + CDK4/6 inhibitors in first line HR+/HER2- metastatic breast cancer (MBC) patients. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-37.

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Price, Sarah, Molly Schumer, Rebecca L. Young, Silu Wang et Molly Cummings. « Immune genomic response associated with preference behavior : an examination in a freshwater fish ». Journal of Immunology 204, n^o 1_Supplement (1 mai 2020) : 92.34. http://dx.doi.org/10.4049/jimmunol.204.supp.92.34.

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Abstract Immune activity in the brain underlies many social behaviors. This immune-behavior relationship can be viewed under a genomics scope by isolating transcriptomic correlates and molecular pathways present following various social encounters. Here we explore how immune genes correlate with different social exposures: mate-choice and social affiliation. Using an established model for sexual selection studies, we compared the immune gene responses in female brains following exposure to either a potential mate or a conspecific female. Females from the Poeciliidae family of fishes, the sailfin molly (Poecilia latipinna), were profiled for their social preference behavior and brain transcriptomes using RNA-seq. During the 30 minute behavioral assay, females were placed into one of two groups: (n=8) given the choice of a large male and small male (‘mate choice’) or a choice between a large and small female (n=8; ‘social affiliation’). The relationship between immune gene responses (categorized using Gene Ontology analysis) and behavior (preference, social affiliation, activity) will be explored using a linear model approach for differential expression (limma; Ritchie ME, et al, 2015) and WGCNA (weighted gene co-expression network analysis; Langfelder & Horvath, 2008). The RNA-seq transcriptomes from each female (n=16) will be analyzed by comparing differential expression between the two groups (‘mate-choice’ vs ‘social preference’).

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Zhao, Xingtang, Lei Yu, Zhang Liu, Jianfei Liu, Xintong Ji, Xu Zhang, Mengqi Liu, Yushuo Mei, Fansuo Zeng et Yaguang Zhan. « Transcriptome Analysis for Fraxinus mandshurica Rupr. Seedlings from Different Carbon Sequestration Provenances in Response to Nitrogen Deficiency ». Forests 12, n^o 2 (23 février 2021) : 257. http://dx.doi.org/10.3390/f12020257.

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To explore the molecular regulatory mechanism of high-carbon (C) sequestration Fraxinus mandshurica Rupr. (F. mandshurica) provenance and the expression profile of F. mandshurica during nitrogen (N) starvation, the foliage and roots of the annual Wuchang (WC) seedlings with greater C amount and Hailin (HL) seedlings with smaller C amount, which were grown in N-deficient nutrition and complete N, were used for RNA-seq and physiological determination, respectively. One thousand and fifty-seven differentially expressed genes (DEGs) between WC and HL and 8173 DEGs related to N deficiency were identified, respectively. The root of F. mandshurica responded to N deficiency more strongly than foliar. The target genes that responded to N deficiency in roots were mainly regulatory genes (transcription factors, hormones and protein kinases), and their response patterns were upregulated. The growth and N concentration in both WC and HL were reduced by the N deficiency, which might result from the decrease of the leaf Nitrate reductase (NR) and glutamine synthetase (GS) enzyme activity and ABA content, although the root-to-shoot ratio; lateral root number; lignin content; endogenous hormones content (GA, IAA and ZR); root GS and glutamate synthetase activity and transcriptional level of most of the regulatory genes were increased. The C sequestration capacity in WC was greater than that in HL, which related to the higher GS enzymes activity and transcriptional levels of regulatory genes and metabolic genes (terpenes, carbohydrates, and lipid energy). However, the C sequestration advantage of WC was significantly reduced by the N deficiency, which was due to the smaller response to N deficiency compared to HL.

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Xu, Min, Can-Bin Zeng, Rui He, Zhen Yan, Zhao Qi, Rui Xiong, Yu Cheng, Shuang-Shuang Wei et Hua Tang. « Transcriptome Analysis of Banana (Musa acuminate L.) in Response to Low-Potassium Stress ». Agronomy 9, n^o 4 (29 mars 2019) : 169. http://dx.doi.org/10.3390/agronomy9040169.

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Potassium (K+) is an abundant and important macronutrient for plants. It plays crucial roles in many growth and developmental processes, and growth is inhibited under low −K+ conditions. The molecular mechanisms operating under K+ starvation have been little reported in banana, which is a non-model plant. We conducted a transcriptome analysis of banana (Musa acuminata L. AAA group, cv. Cavendish) in response to low −K+ stress. The phenotypic traits and transcriptomic profiles of banana leaves and roots were compared between low −K+ (LK) and normal −K+ (NK) groups. The phenotypic parameters for the LK group, including fresh and dry weight, were lower than those for the NK group, which suggested that low −K+ stress may inhibit some important metabolic and biosynthetic processes. K+ content and biomass were both decreased in the LK group compared to the NK group. Following ribonucleic acid sequencing (RNA-Seq), a total of 26,796 expressed genes were detected in normal −K+ leaves (NKL), 27,014 were detected in low −K+ leaves (LKL), 29,158 were detected in normal −K+ roots (NKR), and 28,748 were detected in low −K+ roots (LKR). There were 797 up-regulated differentially expressed genes (DEGs) and 386 down-regulated DEGs in NKL versus LKL, while there were 1917 up-regulated DEGs and 2830 down-regulated DEGs in NKR versus LKR. This suggested that the roots were more sensitive to low −K+ stress than the leaves. DEGs related to K+ transport and uptake were analyzed in detail. Gene functional classification showed that the expression of genes regarding ABC transporters, protein kinases, transcription factors, and ion transporters were also detected, and may play important roles during K+ deficiency.

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dos Santos, Sandra C., Sandra Tenreiro, Margarida Palma, Jorg Becker et Isabel Sá-Correia. « Transcriptomic Profiling of the Saccharomyces cerevisiae Response to Quinine Reveals a Glucose Limitation Response Attributable to Drug-Induced Inhibition of Glucose Uptake ». Antimicrobial Agents and Chemotherapy 53, n^o 12 (5 octobre 2009) : 5213–23. http://dx.doi.org/10.1128/aac.00794-09.

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ABSTRACT Quinine has been employed in the treatment of malaria for centuries and is still used against severe Plasmodium falciparum malaria. However, its interactions with the parasite remain poorly understood and subject to debate. In this study, we used the Saccharomyces cerevisiae eukaryotic model to better understand quinine's mode of action and the mechanisms underlying the cell response to the drug. We obtained a transcriptomic profile of the yeast's early response to quinine, evidencing a marked activation of genes involved in the low-glucose response (e.g., CAT8, ADR1, MAL33, MTH1, and SNF3). We used a low inhibitory quinine concentration with no detectable effect on plasma membrane function, consistent with the absence of a general nutrient starvation response and suggesting that quinine-induced glucose limitation is a specific response. We have further shown that transport of [14C]glucose is inhibited by quinine, with kinetic data indicating competitive inhibition. Also, tested mutant strains deleted for genes encoding high- and low-affinity hexose transporters (HXT1 to HXT5, HXT8, and HXT10) exhibit resistance phenotypes, correlating with reduced levels of quinine accumulation in the mutants examined. These results suggest that the hexose transporters are facilitators of quinine uptake in S. cerevisiae, possibly through a competitive inhibition mechanism. Interestingly, P. falciparum is highly dependent on glucose uptake, which is mediated by the single-copy transporter PfHT1, a protein with high homology to yeast's hexose transporters. We propose that PfHT1 is an interesting candidate quinine target possibly involved in quinine import in P. falciparum, an uptake mechanism postulated in recent studies to occur through a still-unidentified importer(s).

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Wang, Chunping, Yifei Li, Wenqin Bai, Xiaomiao Yang, Hong Wu, Kairong Lei, Renzhong Huang, Shicai Zhang, Qizhong Huang et Qing Lin. « Comparative Transcriptome Analysis Reveals Different Low-Nitrogen-Responsive Genes in Pepper Cultivars ». Horticulturae 7, n^o 5 (13 mai 2021) : 110. http://dx.doi.org/10.3390/horticulturae7050110.

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The molecular mechanisms underlying the variation in N-use efficiency (NUE) in pepper (Capsicum annuum L.) genotypes are poorly understood. In this work, two genotypes (750-1, low-N tolerant; ZCFB, low-N sensitive) with contrasting low-N tolerance were selected from 100 pepper cultivars on the basis of their relative leaf areas, shoot dry weights, root dry weights, and plant dry weights at the seedling stage. Subsequently, using RNA-Seq, the transcriptome of these two pepper genotypes under N starvation for 28 days was analyzed. We detected 2621/2470 and 3936/4218 different expressed genes (DEGs) in the leaves/roots of 750-1 and ZCFB, respectively. The changes in the expression of basic N metabolism genes were similar between 750-1 and ZCFB. However, different DEGs not directly involved in N metabolism were identified between the 750-1 and ZCFB cultivars. In 750-1, 110 unique DEGs were detected in the leaves, of which 103 were down-regulated, including genes associated with protein metabolism, photosynthesis, secondary metabolism, cell wall metabolism, stress response, and disease resistance. In ZCFB, 142 unique DEGs were detected in the roots, of which 117 were up-regulated, resulting in enhancement of processes such as protein degradation, secondary metabolites synthesis, lipid metabolism, endocytosis, the tricarboxylic acid cycle (TCA), transcriptional regulation, stress response, and disease resistance. Our results not only facilitate an understanding of the different regulatory process in low-N-tolerant and low-N-sensitive pepper cultivars, but also provide abundant candidate genes for improving the low-N tolerance of pepper cultivars.

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Tan, Longtao, Gang Gao, Chunming Yu, Aiguo Zhu, Ping Chen, Kunmei Chen, Jikang Chen et Heping Xiong. « Transcriptome Analysis of High-NUE (T29) and Low-NUE (T13) Genotypes Identified Different Responsive Patterns Involved in Nitrogen Stress in Ramie (Boehmeria nivea (L.) Gaudich) ». Plants 9, n^o 6 (19 juin 2020) : 767. http://dx.doi.org/10.3390/plants9060767.

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Nitrogen-use efficiency (NUE) has significant impacts on plant growth and development. NUE in plants differs substantially in physiological resilience to nitrogen stress; however, the molecular mechanisms underlying enhanced resilience of high-NUE plants to nitrogen deficiency remains unclear. We compared transcriptome-wide gene expression between high-NUE and low-NUE ramie (Boehmeria nivea (L.) Gaudich) genotypes under nitrogen (N)-deficient and normal conditions to identify the transcriptomic expression patterns that contribute to ramie resilience to nitrogen deficiency. Two ramie genotypes with contrasting NUE were used in the study, including T29 (NUE = 46.01%) and T13 (NUE = 15.81%). Our results showed that high-NUE genotypes had higher gene expression under the control condition across 94 genes, including frontloaded genes such as GDSL esterase and lipase, gibberellin, UDP-glycosyltransferase, and omega-6 fatty acid desaturase. Seventeen stress-tolerance genes showed lower expression levels and varied little in response to N-deficiency stress in high-NUE genotypes. In contrast, 170 genes were upregulated under N deficiency in high-NUE genotypes but downregulated in low-NUE genotypes compared with the controls. Furthermore, we identified the potential key genes that enable ramie to maintain physiological resilience under N-deficiency stress, and categorized these genes into three groups based on the transcriptome and their expression patterns. The transcriptomic and clustering analysis of these nitrogen-utilization-related genes could provide insight to better understand the mechanism of linking among the three gene classes that enhance resilience in high-NUE ramie genotypes.

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Passaro, C., D. Tutt, S. Bagés-Arnal, C. Maicas, R. Laguna-Barraza, A. Gutierrez-Adán, J. A. Browne et al. « Global transcriptomic response of bovine endometrium to blastocyst-stage embryos ». Reproduction 158, n^o 3 (septembre 2019) : 223–35. http://dx.doi.org/10.1530/rep-19-0064.

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The aims of this study were (i) to investigate changes in the global transcriptome of bovine endometrial explants induced by exposure to blastocysts, (ii) to investigate if male and female blastocysts elicit a differential response in the endometrial transcriptome in vitro and (iii) to determine whether bovine endometrium responds to the presence of murine embryos. In Experiment 1, endometrial explants from the same uterus were cultured for 6 h with or without 20 in vitro-produced bovine blastocysts. In Experiment 2, endometrial explants were cultured with male or female bovine blastocysts produced in vitro by IVF either using sex-sorted semen or conventional unsorted semen followed by embryo sexing based on a biopsy. In Experiment 3, endometrial explants were cultured alone or in the presence of bovine blastocysts (n = 25) or murine blastocysts (n = 25). Following culture, explants were snap frozen and stored at −80°C until RNA extraction, qPCR or RNA-Seq. Culture with bovine blastocysts increased endometrial expression of 40 transcripts, all of which were interferon-tau induced. Culture with male or female bovine blastocysts increased transcript abundance of five classic interferon-stimulated genes (MX1, MX2, ISG15, OASY1, RSAD2) in explants; however, there was no difference in abundance of transcripts previously reported to be related to embryonic sex (IFNAR1, IFNAR2, CTGF, ARTN, SLC2A1, SLC2A5). Exposure to murine blastocysts did not elicit any detectable change in transcript abundance. These findings, coupled with our previous data, indicate that very local, interferon-tau-induced changes in endometrial gene expression occur in response to blastocysts; whether such changes play any role in subsequent pregnancy recognition remains to be established.

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Fuentes-Merlos, Maria Isabel, Masaru Bamba, Shusei Sato et Atsushi Higashitani. « Comparative Transcriptome Analysis of Grafted Tomato with Drought Tolerance ». Plants 11, n^o 15 (27 juillet 2022) : 1947. http://dx.doi.org/10.3390/plants11151947.

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Grafting is a method used in agriculture to improve crop production and tolerance to biotic and abiotic stress. This technique is widely used in tomato, Solanum lycopersicum L.; however, the effects of grafting on changes in gene expression associated with stress tolerance in shoot apical meristem cells are still under-discovered. To clarify the effect of grafting, we performed a transcriptomic analysis between non-grafted and grafted tomatoes using the tomato variety Momotaro-scion and rootstock varieties, TD1, GS, and GF. Drought tolerance was significantly improved not only by a combination of compatible resistant rootstock TD1 but also by self-grafted compared to non-grafted lines. Next, we found the differences in gene expression between grafted and non-grafted plants before and during drought stress treatment. These altered genes are involved in the regulation of plant hormones, stress response, and cell proliferation. Furthermore, when comparing compatible (Momo/TD1 and Momo/Momo) and incompatible (Momo/GF) grafted lines, the incompatible line reduced gene expression associated with phytohormones but increased in wounding and starvation stress-response genes. These results conclude that grafting generates drought stress tolerance through several gene expression changes in the apical meristem.

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Zhang, Jiaren, Bob Zimmermann, Giuseppe Galletti, Susan Halabi, Ada Gjyrezi, Qian Yang, Santosh Gupta et al. « Association of circulating tumor cell RB1 loss RNA signature with outcomes and immune phenotypes in men with mCRPC. » Journal of Clinical Oncology 40, n^o 6_suppl (20 février 2022) : 139. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.139.

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139 Background: Androgen receptor signaling inhibitors (ARSi) are a mainstay for patients with metastatic castration-resistant prostate cancer (mCRPC). However, patient response is heterogeneous and the molecular underpinnings of ARSi resistance are not well elucidated. Methods: We performed transcriptome analysis of circulating tumor cells (CTCs) and peripheral blood mononuclear cells (PBMC) in the context of PROPHECY, a prospective clinical trial of men (n = 118) with mCRPC treated with abiraterone (Abi) or enzalutamide (Enza). We obtained CTCs at baseline (before treatment) and at the time of progression on Abi/Enza, performed a comprehensive transcriptomic analysis of CTC patient samples (n = 40) and correlated with clinical outcomes to identify mechanisms of ARSi resistance. In addition, we also performed a transcriptomic analysis of matching peripheral blood mononuclear cells (PBMCs) in order to uncover potential involvement of the circulating immune macroenvironment (CIME) in ARSi resistance. The proportional hazard model was used to determine the prognostic significance of these signatures in predicting overall survival (OS) and progression-free survival (PFS). Results: CTC RNA-sequencing identified that RB loss concurrently with enhanced E2F signaling transcriptional networks were associated with intrinsic ARSi resistance. Using single sample GSEA (ssGSEA) score, we identified that the RB/E2F common signature at baseline was associated with short PFS (median PFS = 6.5 months) and OS (median OS = 24.5 months) (hazard ratio (HR) = 3.5; 95% CI 1.5-8.2) in men with mCRPC. We further developed a BRCA loss transcriptional signature which we validated in the SU2C mCRPC patient cohort, by showing that BRCA loss transcriptional network reflected BRCA genomic alterations as it was significantly enriched in the SU2C BRCA-altered patients vs unaltered patients. Generating BRCA loss ssGSEA scores in the PROPHECY cohort we observed that patients with high BRCA loss scores at baseline experienced shorter OS (HR = 2.42; 95% CI = 1-5.9). Through the comparison of CTC transcriptomic profiles at progression with baseline, we identified an inflammatory response signature in CTCs which was significantly associated with acquired ARSi resistance. Transcriptomic analysis of matching PBMCs identified enrichment of inflammasome gene signatures indicative of activated innate immunity at progression, with concurrent downregulation of CD8 T and NK cells. Importantly, CTC gene signatures of RB loss/E2F signaling had a significant positive association with this CIME signatures. Conclusions: Taken together, these data demonstrate that liquid biopsy transcriptomics of both tumor cells and immune cells can identify molecular pathways associated with clinical ARSi resistance paving the way for treatment optimization and the development of novel precision therapies in patients with mCRPC.

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Malesevic, Jelena, Milorad Kojic, Stefan Stanovcic, Natalija Azanjac et Mira Milisavljevic. « Identification of Genes Promoting Growth of Ustilago maydis on Biomolecules Released from Cells Killed by Oxidation ». Journal of Fungi 8, n^o 9 (13 septembre 2022) : 957. http://dx.doi.org/10.3390/jof8090957.

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Much headway has been made in understanding the numerous strategies that enable microorganisms to counteract various types of environmental stress, but little is known about how microbial populations recover after a massive death caused by exposure to extreme conditions. Using the yeast-like fungus Ustilago maydis as a model, our recent post-stress regrowth under starvation (RUS) studies have demonstrated that this organism reconstitutes devastated populations with remarkable efficiency. Subsequently, we have identified four RUS-gene products. Two of these, Did4 and Tbp1, play parallel roles in protecting the genome. To identify additional molecular components, we took a molecular-genetic and a transcriptomic approach. By employing a simple and novel screening method, we identified five RUS-deficient mutants (snf8, slm1, vrg4, snf5, hsf1), three of which (snf8, slm1, and hsf1) displayed sensitivity to different genotoxic agents, indicating that the corresponding gene products have roles in genome protection. The global transcriptomic changes of cells grown in supernatants derived from peroxide-treated cell suspensions revealed sets of uniquely expressed genes. Importantly, among the genes induced by the substrates was Chk1, which encodes a protein kinase required for checkpoint-mediated cell cycle arrest in response to DNA damage. Mutants of U. maydis deleted of Chk1 are severely incapacitated in RUS.

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Ávila-Pérez, Marcela, Jeroen B. van der Steen, Remco Kort et Klaas J. Hellingwerf. « Red Light Activates the σB-Mediated General Stress Response of Bacillus subtilis via the Energy Branch of the Upstream Signaling Cascade ». Journal of Bacteriology 192, n^o 3 (30 novembre 2009) : 755–62. http://dx.doi.org/10.1128/jb.00826-09.

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ABSTRACT The σB-dependent general stress response in the common soil bacterium Bacillus subtilis can be elicited by a range of stress factors, such as starvation or an ethanol, salt, or heat shock, via a complex upstream signaling cascade. Additionally, σB can be activated by blue light via the phototropin homologue YtvA, a component of the environmental branch of the signaling cascade. Here we use a reporter-gene fusion to show that σB can also be activated by red light via the energy branch of its upstream signaling cascade. Deletion mutagenesis and homologous overproduction experiments indicate that the RsbP protein (composed of an N-terminal Per-ARNT-Sim [PAS] domain and a C-terminal PP2C-type phosphatase domain) is involved in the red light response. This second light input pathway functions complementarily to YtvA; it shows broader spectral sensitivity but requires higher light intensities. These results are confirmed by transcriptome analyses, which show that both light effects result in upregulation of the σB regulon, with minimal activation of other responses.

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Si, Lingjun, Luqing Pan, Hongdan Wang et Xin Zhang. « Transcriptomic response to ammonia-N stress in the hepatopancreas of swimming crab Portunus trituberculatus ». Marine Life Science & ; Technology 2, n^o 2 (16 mars 2020) : 135–45. http://dx.doi.org/10.1007/s42995-020-00033-3.

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Stergiopoulos, Konstantinos, Pablo Cabrero, Shireen-Anne Davies et Julian A. T. Dow. « Salty dog, an SLC5 symporter, modulatesDrosophilaresponse to salt stress ». Physiological Genomics 37, n^o 1 (mars 2009) : 1–11. http://dx.doi.org/10.1152/physiolgenomics.90360.2008.

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To regulate their internal environments, organisms must adapt to varying ion levels in their diet. Adult Drosophila were exposed to dietary salt stress, and their physiological, survival, and gene expression responses monitored. Insects continued to feed on NaCl-elevated diet, although levels >4% wt/vol ultimately proved fatal. Affymetrix microarray analysis of flies fed on diet containing elevated NaCl showed a phased response: the earliest response was widespread upregulation of immune genes, followed by upregulation of carbohydrate metabolism as the immune response was downregulated, then finally a switch to amino acid catabolism and inhibition of genes associated with the reproductive axis. Significantly, the online transcriptomic resource FlyAtlas reports that most of the modulated genes are predominantly expressed in hindgut or Malpighian (renal) tubule, implicating these excretory tissues as the major responders to salt stress. Three genes were selected for further study: the SLC5 symporter CG2196, the GLUT transporter CG6484, and the transcription factor sugarbabe (previously implicated in starvation and stress responses). Expression profiles predicted by microarray were validated by quantitative PCR (qPCR); expression was mapped to the alimentary canal by in situ hybridization. CG2196::eYFP overexpression constructs were localized to the basolateral membrane of the Malpighian (renal) tubules, and RNAi against CG2196 improved survival on high-salt diet, even when driven specifically to just principal cells of the Malpighian tubule, confirming both this tissue and this transporter as major determinants of survival upon salt stress. Accordingly, CG2196 was renamed salty dog ( salt).

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Courbet, Galatéa, Aurélien D’Oria, Anne Maillard, Lun Jing, Sylvain Pluchon, Mustapha Arkoun, Stéphanie Pateyron et al. « Comparative Omics Analysis of Brassica napus Roots Subjected to Six Individual Macronutrient Deprivations Reveals Deficiency-Specific Genes and Metabolomic Profiles ». International Journal of Molecular Sciences 22, n^o 21 (28 octobre 2021) : 11679. http://dx.doi.org/10.3390/ijms222111679.

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The early and specific diagnosis of a macronutrient deficiency is challenging when seeking to better manage fertilizer inputs in the context of sustainable agriculture. Consequently, this study explored the potential for transcriptomic and metabolomic analysis of Brassica napus roots to characterize the effects of six individual macronutrient deprivations (N, Mg, P, S, K, and Ca). Our results showed that before any visual phenotypic response, all macronutrient deprivations led to a large modulation of the transcriptome and metabolome involved in various metabolic pathways, and some were common to all macronutrient deprivations. Significantly, comparative transcriptomic analysis allowed the definition of a subset of 3282, 2011, 6325, 1384, 439, and 5157 differentially expressed genes (DEGs) specific to N, Mg, P, S, K, and Ca deprivations, respectively. Surprisingly, gene ontology term enrichment analysis performed on this subset of specific DEGs highlighted biological processes that are common to a number of these macronutrient deprivations, illustrating the complexity of nutrient interactions. In addition, a set of 38 biochemical compounds that discriminated the macronutrient deprivations was identified using a metabolic approach. The opportunity to use these specific DEGs and/or biochemical compounds as potential molecular indicators to diagnose macronutrient deficiency is discussed.

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Zeng, Congli, Gabriel C. Motta-Ribeiro, Takuga Hinoshita, Marcos Adriano Lessa, Tilo Winkler, Kira Grogg, Nathan M. Kingston et al. « Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep ». Anesthesiology 133, n^o 5 (7 août 2020) : 1060–76. http://dx.doi.org/10.1097/aln.0000000000003491.

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Background Pulmonary atelectasis is frequent in clinical settings. Yet there is limited mechanistic understanding and substantial clinical and biologic controversy on its consequences. The authors hypothesize that atelectasis produces local transcriptomic changes related to immunity and alveolar–capillary barrier function conducive to lung injury and further exacerbated by systemic inflammation. Methods Female sheep underwent unilateral lung atelectasis using a left bronchial blocker and thoracotomy while the right lung was ventilated, with (n = 6) or without (n = 6) systemic lipopolysaccharide infusion. Computed tomography guided samples were harvested for NextGen RNA sequencing from atelectatic and aerated lung regions. The Wald test was used to detect differential gene expression as an absolute fold change greater than 1.5 and adjusted P value (Benjamini–Hochberg) less than 0.05. Functional analysis was performed by gene set enrichment analysis. Results Lipopolysaccharide-unexposed atelectatic versus aerated regions presented 2,363 differentially expressed genes. Lipopolysaccharide exposure induced 3,767 differentially expressed genes in atelectatic lungs but only 1,197 genes in aerated lungs relative to the corresponding lipopolysaccharide-unexposed tissues. Gene set enrichment for immune response in atelectasis versus aerated tissues yielded negative normalized enrichment scores without lipopolysaccharide (less than –1.23, adjusted P value less than 0.05) but positive scores with lipopolysaccharide (greater than 1.33, adjusted P value less than 0.05). Leukocyte-related processes (e.g., leukocyte migration, activation, and mediated immunity) were enhanced in lipopolysaccharide-exposed atelectasis partly through interferon-stimulated genes. Furthermore, atelectasis was associated with negatively enriched gene sets involving alveolar–capillary barrier function irrespective of lipopolysaccharide (normalized enrichment scores less than –1.35, adjusted P value less than 0.05). Yes-associated protein signaling was dysregulated with lower nuclear distribution in atelectatic versus aerated lung (lipopolysaccharide-unexposed: 10.0 ± 4.2 versus 13.4 ± 4.2 arbitrary units, lipopolysaccharide-exposed: 8.1 ± 2.0 versus 11.3 ± 2.4 arbitrary units, effect of lung aeration, P = 0.003). Conclusions Atelectasis dysregulates the local pulmonary transcriptome with negatively enriched immune response and alveolar–capillary barrier function. Systemic lipopolysaccharide converts the transcriptomic immune response into positive enrichment but does not affect local barrier function transcriptomics. Interferon-stimulated genes and Yes-associated protein might be novel candidate targets for atelectasis-associated injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Cheng, Chi-Hua, Bing-Nan Shen, Qian-Wen Shang, Li-Yu Daisy Liu, Kou-Cheng Peng, Yan-Huey Chen, Fang-Fang Chen et al. « Gene-to-Gene Network Analysis of the Mediation of Plant Innate Immunity by the Eliciting Plant Response-Like 1 (Epl1) Elicitor of Trichoderma formosa ». Molecular Plant-Microbe Interactions® 31, n^o 7 (juillet 2018) : 683–91. http://dx.doi.org/10.1094/mpmi-01-18-0002-ta.

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A new clade, Trichoderma formosa, secretes eliciting plant response-like 1 (Epl1), a small peptide elicitor that stimulates plant immunity. Nicotiana benthamiana pretreated with Epl1 for 3 days developed immunity against Tomato mosaic virus (ToMV) infection. The transcriptome profiles of T. formosa and N. benthamiana were obtained by deep sequencing; the transcript of Epl1 is 736 nt in length and encodes a 12-kDa peptide. Identifying critical genes in Epl1-mediated immunity was challenging due to high similarity between the transcriptome expression profiles of Epl1-treated and ToMV-infected N. benthamiana samples. Therefore, an efficient bioinformatics data mining approach was used for high-throughput transcriptomic assays in this study. We integrated gene-to-gene network analysis into the ContigViews transcriptome database, and genes related to jasmonic acid and ethylene signaling, salicylic acid signaling, leucine-rich repeats, transcription factors, and histone variants were hubs in the gene-to-gene networks. In this study, the Epl1 of T. formosa triggers plant immunity against various pathogen infections. Moreover, we demonstrated that high-throughput data mining and gene-to-gene network analysis can be used to identify critical candidate genes for further studies on the mechanisms of plant immunity.

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Zhang, Jiaren, Bob Zimmermann, Giuseppe Galletti, Susan Halabi, Ada Gjyrezi, Qian Yang, Santosh Gupta et al. « Abstract 646 : Liquid biopsy transcriptomics identify pathways associated with poor outcomes and immune phenotypes in men with mCRPC ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : 646. http://dx.doi.org/10.1158/1538-7445.am2022-646.

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Abstract Androgen receptor signaling inhibitors (ARSi) and taxanes are mainstays for patients with metastatic castration-resistant prostate cancer (mCRPC). However, patient response is heterogeneous, and the molecular underpinnings of treatment resistance are not well elucidated. To identify clinically meaningful mechanisms of treatment resistance, we performed transcriptome analysis of circulating tumor cells (CTCs) isolated from mCRPC patients enrolled in two independent prospective clinical trials: PROPHECY, a clinical study of patients (n=118) treated with abiraterone or enzalutamide followed by docetaxel; and TAXYNERGY where patients were randomized to docetaxel or cabazitaxel treatment. CTCs were obtained at baseline (before treatment), on treatment and at progression and their comprehensive transcriptomic analysis was correlated with clinical outcomes. To uncover potential involvement of the circulating immune macroenvironment (CIME) in treatment resistance, we performed transcriptomic analysis of matching peripheral blood mononuclear cells (PBMCs) using an established, rigorous, blood-derived transcriptional modular framework. In PROPHECY, CTC RNA-seq identified that RB loss concurrently with enhanced E2F signaling networks were associated with intrinsic ARSi resistance. Using single sample GSEA (ssGSEA) score, we identified that the RB/E2F common signature at baseline was associated with short PFS (median PFS=6.5 months) and OS (median OS=24.5 months) (hazard ratio (HR) = 3.5; 95% CI 1.5-8.2) in men with mCRPC. We further developed a BRCA-loss transcriptional signature, and validated it in the SU2C mCRPC patient cohort, expanding the identification of patients with BRCA-loss phenotypes beyond genomic loss. Applying this signature to PROPHECY baseline samples, we showed that men with high BRCA-loss scores experienced shorter OS (HR=2.42; 95% CI=1-5.9). Through the comparison of CTC transcriptomic profiles at progression with baseline, we identified an inflammatory response signature in CTCs which was significantly associated with acquired ARSi resistance. Transcriptomic PBMC analysis further identified enrichment of inflammasome gene signatures at progression, with concurrent downregulation of CD8+ T and NK cells. Furthermore, preliminary data from both clinical trials, showed a significant upregulation of TGF-β1 and corresponding TGFβ-Receptor signaling pathway in CTCs from patients at progression following taxane treatment, suggesting a role for TGFβ pathway in clinical response to taxane chemotherapy. Taken together, these data demonstrate that liquid biopsy transcriptomics of both tumor cells and immune cells can identify molecular pathways associated with treatment resistance paving the way for treatment optimization and the development of novel precision therapies in patients with mCRPC. Citation Format: Jiaren Zhang, Bob Zimmermann, Giuseppe Galletti, Susan Halabi, Ada Gjyrezi, Qian Yang, Santosh Gupta, Akanksha Verma, Andrea Sboner, Monika Anand, Daniel J. George, Simon G. Gregory, Prerna Mahtani, Seunghee Hong, Virginia Pascual, Clio P. Mavragani, Emmanuel S. Antonarakis, David M. Nanus, Scott T. Tagawa, Olivier Elemento, Andrew J. Armstrong, Paraskevi Giannakakou. Liquid biopsy transcriptomics identify pathways associated with poor outcomes and immune phenotypes in men with mCRPC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 646.

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Estravis-Barcala, Maximiliano, Katrin Heer, Paula Marchelli, Birgit Ziegenhagen, María Verónica Arana et Nicolás Bellora. « Deciphering the transcriptomic regulation of heat stress responses in Nothofagus pumilio ». PLOS ONE 16, n^o 3 (30 mars 2021) : e0246615. http://dx.doi.org/10.1371/journal.pone.0246615.

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Global warming is predicted to exert negative impacts on plant growth due to the damaging effect of high temperatures on plant physiology. Revealing the genetic architecture underlying the heat stress response is therefore crucial for the development of conservation strategies, and for breeding heat-resistant plant genotypes. Here we investigated the transcriptional changes induced by heat in Nothofagus pumilio, an emblematic tree species of the sub-Antarctic forests of South America. Through the performance of RNA-seq of leaves of plants exposed to 20°C (control) or 34°C (heat shock), we generated the first transcriptomic resource for the species. We also studied the changes in protein-coding transcripts expression in response to heat. We found 5,214 contigs differentially expressed between temperatures. The heat treatment resulted in a down-regulation of genes related to photosynthesis and carbon metabolism, whereas secondary metabolism, protein re-folding and response to stress were up-regulated. Moreover, several transcription factor families like WRKY or ERF were promoted by heat, alongside spliceosome machinery and hormone signaling pathways. Through a comparative analysis of gene regulation in response to heat in Arabidopsis thaliana, Populus tomentosa and N. pumilio we provide evidence of the existence of shared molecular features of heat stress responses across angiosperms, and identify genes of potential biotechnological application.

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Fadul, Motaz M., Paul R. Heath, Johnathan Cooper-Knock, Julian M. Kurz, Hayder A. Al-Azzawi, Zarki Ali, Taylor Smith et al. « Transcriptomic Analysis of Age-Associated Periventricular Lesions Reveals Dysregulation of the Immune Response ». International Journal of Molecular Sciences 21, n^o 21 (25 octobre 2020) : 7924. http://dx.doi.org/10.3390/ijms21217924.

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White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as “pre-lesional.” Microarray analysis identified 2256 significantly differentially-expressed genes (p ≤ 0.05, FC ≥ 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in “pre-lesional” cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in “pre-lesional” versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of “pre-lesional” periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL.

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