Bibliographies thématiques / Organoides corticaux

Littérature scientifique sur le sujet « Organoides corticaux »

Auteur : Grafiati

Publié le 13 juillet 2024

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Articles de revues sur le sujet "Organoides corticaux"

Bao, Zhongyuan, Kaiheng Fang, Zong Miao, Chong Li, Chaojuan Yang, Qiang Yu, Chen Zhang, Zengli Miao, Yan Liu et Jing Ji. « Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice ». Oxidative Medicine and Cellular Longevity 2021 (22 novembre 2021) : 1–16. http://dx.doi.org/10.1155/2021/6338722.

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Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice’s spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.

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Camp, J. Gray, Farhath Badsha, Marta Florio, Sabina Kanton, Tobias Gerber, Michaela Wilsch-Bräuninger, Eric Lewitus et al. « Human cerebral organoids recapitulate gene expression programs of fetal neocortex development ». Proceedings of the National Academy of Sciences 112, n^o 51 (7 décembre 2015) : 15672–77. http://dx.doi.org/10.1073/pnas.1520760112.

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Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

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Yang, Woo Sub, Ferdi Ridvan Kiral et In-Hyun Park. « Telencephalic organoids as model systems to study cortical development and diseases ». Organoid 4 (25 janvier 2024) : e1. http://dx.doi.org/10.51335/organoid.2024.4.e1.

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The telencephalon is the largest region of the brain and processes critical brain activity. Despite much progress, our understanding of the telencephalon’s function, development, and pathophysiological processes remains largely incomplete. Recently, 3-dimensional brain models, known as brain organoids, have attracted considerable attention in modern neurobiological research. Brain organoids have been proven to be valuable for studying the neurodevelopmental principles and pathophysiology of the brain, as well as for developing potential therapeutics. Brain organoids can change the paradigm of current research, replacing animal models. However, there are still limitations, and efforts are needed to improve brain organoid models. In this review, we provide an overview of the development and function of the telencephalon, as well as the techniques and scientific methods used to create fully developed telencephalon organoids. Additionally, we explore the limitations and challenges of current brain organoids and potential future advancements.

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Revah, Omer, Felicity Gore, Kevin W. Kelley, Jimena Andersen, Noriaki Sakai, Xiaoyu Chen, Min-Yin Li et al. « Maturation and circuit integration of transplanted human cortical organoids ». Nature 610, n^o 7931 (12 octobre 2022) : 319–26. http://dx.doi.org/10.1038/s41586-022-05277-w.

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AbstractSelf-organizing neural organoids represent a promising in vitro platform with which to model human development and disease1–5. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.

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Magni, Manuela, Beatrice Bossi, Paola Conforti, Maura Galimberti, Fabio Dezi, Tiziana Lischetti, Xiaoling He et al. « Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models ». International Journal of Molecular Sciences 23, n^o 21 (29 octobre 2022) : 13159. http://dx.doi.org/10.3390/ijms232113159.

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In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.

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Chandrasegaran, Praveena, Agatha Nabilla Lestari, Matthew C. Sinton, Jay Gopalakrishnan et Juan F. Quintana. « Modelling host-Trypanosoma brucei gambiense interactions in vitro using human induced pluripotent stem cell-derived cortical brain organoids ». F1000Research 12 (28 juillet 2023) : 437. http://dx.doi.org/10.12688/f1000research.131507.2.

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Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and is associated with neuroinflammation and neuropsychiatric disorders, including disruption of sleep/wake patterns, and is now recognised as a circadian disorder. Sleeping sickness is traditionally studied using murine models of infection due to the lack of alternative in vitro systems that fully recapitulate the cellular diversity and functionality of the human brain. The aim of this study is to develop a much-needed in vitro system that reduces and replaces live animals for the study of infections in the central nervous system, using sleeping sickness as a model infection. Methods: We developed a co-culture system using induced pluripotent stem cell (iPSC)-derived cortical human brain organoids and the human pathogen T. b. gambiense to model host-pathogen interactions in vitro. Upon co-culture, we analysed the transcriptional responses of the brain organoids to T. b. gambiense over two time points. Results: We detected broad transcriptional changes in brain organoids exposed to T. b. gambiense, mainly associated with innate immune responses, chemotaxis, and blood vessel differentiation compared to untreated organoids. Conclusions: Our co-culture system provides novel, more ethical avenues to study host-pathogen interactions in the brain as alternative models to experimental infections in mice. Although our data support the use of brain organoids to model host-pathogen interactions during T. brucei infection as an alternative to in vivo models, future work is required to increase the complexity of the organoids ( e.g., addition of microglia and vasculature). We envision that the adoption of organoid systems is beneficial to researchers studying mechanisms of brain infection by protozoan parasites. Furthermore, organoid systems have the potential to be used to study other parasites that affect the brain significantly reducing the number of animals undergoing moderate and/or severe protocols associated with the study of neuroinflammation and brain infections.

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Li, Xiaodong, Abdullah Shopit et Jingmin Wang. « A Comprehensive Update of Cerebral Organoids between Applications and Challenges ». Oxidative Medicine and Cellular Longevity 2022 (5 décembre 2022) : 1–10. http://dx.doi.org/10.1155/2022/7264649.

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The basic technology of stem cells has been developed and created organoids, which have established a strong interest in regenerative medicine. Different cell types have been used to generate cerebral organoids, which include interneurons and oligodendrocytes (OLs). OLs are fundamental for brain development. Abundant studies have displayed that brain organoids can recapitulate fundamental and vital features of the human brain, such as cellular regulation and distribution, neuronal networks, electrical activities, and physiological structure. The organoids contain essential ventral brain domains and functional cortical interneurons, which are similar to the developing cortex and medial ganglionic eminence (MGE). So, brain organoids have provided a singular model to study and investigate neurological disorder mechanisms and therapeutics. Furthermore, the blood brain barrier (BBB) organoids modeling contributes to accelerate therapeutic discovery for the treatment of several neuropathologies. In this review, we summarized the advances of the brain organoids applications to investigate neurological disorder mechanisms such as neurodevelopmental and neurodegenerative disorders, mental disorders, brain cancer, and cerebral viral infections. We discussed brain organoids’ therapeutic application as a potential therapeutic unique method and highlighted in detail the challenges and hurdles of organoid models.

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Conforti, P., D. Besusso, V. D. Bocchi, A. Faedo, E. Cesana, G. Rossetti, V. Ranzani et al. « Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes ». Proceedings of the National Academy of Sciences 115, n^o 4 (8 janvier 2018) : E762—E771. http://dx.doi.org/10.1073/pnas.1715865115.

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Increasing evidence suggests that early neurodevelopmental defects in Huntington’s disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a large CAG expansion causes complete failure of the neuro-ectodermal acquisition, while cells carrying shorter CAGs repeats show gross abnormalities in neural rosette formation as well as disrupted cytoarchitecture in cortical organoids. Gene-expression analysis showed that control organoid overlapped with mature human fetal cortical areas, while HD organoids correlated with the immature ventricular zone/subventricular zone. We also report that defects in neuroectoderm and rosette formation could be rescued by molecular and pharmacological approaches leading to a recovery of striatal identity. These results show that mutant huntingtin precludes normal neuronal fate acquisition and highlights a possible connection between mutant huntingtin and abnormal neural development in HD.

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Chandrasegaran, Praveena, Agatha Nabilla Lestari, Matthew C. Sinton, Jay Gopalakrishnan et Juan F. Quintana. « Modelling host-Trypanosoma brucei gambiense interactions in vitro using human induced pluripotent stem cell-derived cortical brain organoids ». F1000Research 12 (24 avril 2023) : 437. http://dx.doi.org/10.12688/f1000research.131507.1.

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Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and is associated with neuroinflammation and neuropsychiatric disorders, including disruption of sleep/wake patterns, and is now recognised as a circadian disorder. Sleeping sickness is traditionally studied using murine models of infection due to the lack of alternative in vitro systems that fully recapitulate the cellular diversity and functionality of the human brain. The aim of this study is to develop a much-needed in vitro system that reduces and replaces live animals for the study of infections in the central nervous system, using sleeping sickness as a model infection. Methods: We developed a co-culture system using induced pluripotent stem cell (iPSC)-derived cortical human brain organoids and the human pathogen T. b. gambiense to model host-pathogen interactions in vitro. Upon co-culture, we analysed the transcriptional responses of the brain organoids to T. b. gambiense over two time points. Results: We detected broad transcriptional changes in brain organoids exposed to T. b. gambiense, mainly associated with innate immune responses, chemotaxis, and blood vessel differentiation compared to untreated organoids. Conclusions: Our co-culture system provides novel, more ethical avenues to study host-pathogen interactions in the brain as alternative models to experimental infections in mice. Future work is required to increase the complexity of the organoids (e.g., addition of microglia and vasculature). We envision that the adoption of organoid systems will be beneficial to researchers studying mechanisms of brain infection by protozoan parasites. Furthermore, organoid systems have the potential to be used to study other parasites that affect the brain, including neurocysticercosis, significantly reducing the number of animals undergoing moderate and/or severe protocols associated with the study of neuroinflammation and brain infections.

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Sivitilli, Adam A., Jessica T. Gosio, Bibaswan Ghoshal, Alesya Evstratova, Daniel Trcka, Parisa Ghiasi, J. Javier Hernandez, Jean Martin Beaulieu, Jeffrey L. Wrana et Liliana Attisano. « Robust production of uniform human cerebral organoids from pluripotent stem cells ». Life Science Alliance 3, n^o 5 (17 avril 2020) : e202000707. http://dx.doi.org/10.26508/lsa.202000707.

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Human cerebral organoid (hCO) models offer the opportunity to understand fundamental processes underlying human-specific cortical development and pathophysiology in an experimentally tractable system. Although diverse methods to generate brain organoids have been developed, a major challenge has been the production of organoids with reproducible cell type heterogeneity and macroscopic morphology. Here, we have directly addressed this problem by establishing a robust production pipeline to generate morphologically consistent hCOs and achieve a success rate of >80%. These hCOs include both a radial glial stem cell compartment and electrophysiologically competent mature neurons. Moreover, we show using immunofluorescence microscopy and single-cell profiling that individual organoids display reproducible cell type compositions that are conserved upon extended culture. We expect that application of this method will provide new insights into brain development and disease processes.

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Thèses sur le sujet "Organoides corticaux"

Guyomar, Tristan. « Roles of acto-myosin cortex dynamics in organoid self-organisation ». Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAJ100.

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Dans cette thèse, nous étudions les organoïdes, mini-organes auto-assemblés issus de quelques cellules souches, qui offrent une perspective unique pour étudier l'organogenèse. Notre recherche relie les formes et les mouvements collectifs des organoïdes à la dynamique hors équilibre du cortex d’acto-myosine. À l'interface entre la physique et la biologie, nous concevons des expériences pour quantifier les propriétés cellulaires et tissulaires et nous intégrons ces mesures dans des modèles physiques révélant les règles d’auto-organisation des organoïdes. En utilisant des cystes MDCK, un modèle organotypique, nous explorons (i) le rôle des asymétries corticales sur la forme des cellules et du cyste, (ii) comment les protéines de jonction serrée influent sur la morphologie et la mécanique du cyste, et (iii) l'émergence de la rotation collective spontanée en 3D de doublets cellulaires due à la rupture de symétrie de la dynamique d’acto-myosine. Notre travail établit un lien entre l'auto-organisation des organoïdes et la dynamique d’acto-myosine, révélant comment les propriétés hors équilibre dirigent la morphogenèse
In this PhD study, we investigate organoids—self-assembled mini-organs derived from a few stem cells, offering a unique perspective on organogenesis. Our research links organoid shapes and collective motions to the out-of-equilibrium dynamics of the acto-myosin cortex. At the interface between Physics and Biology, we design experiments to quantify cellular and tissue properties and use theoretical physics to integrate measurements into models revealing the self-organization of organoids. Using MDCK cysts, an organotypic model, we explore (i) the role of cortical asymmetries on cell shape and cyst structure, (ii) how tight junction proteins influence cyst morphology and mechanics, and (iii) the emergence of spontaneous 3D collective rotation of cell doublets due to symmetry breaking of acto-myosin dynamics. Our work highlights the intricate link between organoid self-organisation and acto-myosin dynamics further revealing how out-of-equilibrium properties drive morphogenesis

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SKAROS, ADRIANOS. « CEREBRAL CORTICAL GENERIC CIRCUITS SELECTED IN ANATOMICALLY MODERN HUMAN EVOLUTION : A DISSECTION VIA ORTHOGONAL CRISPR PERTURBATIONS ». Doctoral thesis, Università degli Studi di Milano, 2022. https://hdl.handle.net/2434/945932.

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Anatomically modern humans (AMHs) have evolved neural features that differ significantly from those of archaic hominins and underlie their cognitive-behavioural specificities; their evolution, however, has thus far been predominantly inferred from the fossil record and from the comparison of modern and archaic genomes. In doing so, a vast number of genes have been found to harbour changes within protein-coding regions, rendering these different between the AMH genome and Neanderthal and Denisovan genomes. To investigate the functional importance of amino acid changes in the modern human cortex, we prioritise and curate evolutionary- and neurodevelopmentally-relevant genes (15) in order to create a dependency network by combining two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus, to carry out a dual screen in which one gene is activated whilst a second gene is deleted in the same cell; understanding the direction of information flow is vital for characterising how genetic networks affect phenotypes, but also to fully understand single gene functions. Specifically, we integrate hiPSC-based cortical organoid developmental modelling at single cell resolution, multiplex gene editing and gene network reconstruction to enable the first empirically tested, systems-level definition of the molecular logic underlying our recent cortical evolution. We find that five target genes are central to the functional network of perturbed genes, suggesting that the changes in specific genes between AMHs and archaic hominin indeed play a role in cortical evolution and can help understand neurodevelopment.

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Buchsbaum, Isabel Yasmin [Verfasser], et Silvia [Akademischer Betreuer] Cappello. « Discovering novel mechanisms of human cortical development & ; disease using in vivo mouse model and in vitro human-derived cerebral organoids / Isabel Yasmin Buchsbaum ; Betreuer : Silvia Cappello ». München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1215499760/34.

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RIZZUTI, LUDOVICO. « PATIENT-SPECIFIC MODELLING OF SYNDROMIC AUTISM : UNCOVERING THE ROLE OF ADNP IN CHROMATIN DYSREGULATION ». Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/907414.

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ADNP encodes Activity-Dependent Neuroprotective Protein, whose de novo heterozygous mutations cause Helsmoortel-Van der Aa Syndrome (HVDAS), a rare developmental syndrome affecting brain formation and neuronal functions, involving autism spectrum disorder and intellectual disability. Although ADNP is one of the single-gene most frequently mutated in ASD, its precise role in the syndrome onset has yet to be clarified. ADNP is the DNA-binding component of the newly identified chromatin remodeler complex ChAHP in mESC. It recognizes euchromatin regions to establish less accessible local chromatin domains and has also been recently identified as a new player in the regulation of genomic topology, competing with CTCF in the organization of chromatin architecture. Our aim is to understand the genetic and epigenetic implications of ADNP underlying this neurodevelopmental condition; we harnessed cell reprogramming to establish a highly informative cohort of patient-specific iPSCs and use it as a platform to develop meaningful model for the pathology, thus enabling the assessment of the ADNP pivotal relevance in both pluripotent and neuronally-patterned stages. We discovered an altered gene expression program associated with cell fate decision and neuronal lineage commitment, highlighting a neurodevelopmental disruption elicited by ADNP mutations already at the pluripotent stage. Employing CRISPR/Cas9-engineering, we FLAG-tagged the endogenous ADNP to assess its genomic occupancy and revealed a genome-wide distribution of ADNP at gene-regulatory elements and a predominant presence at transposable elements, Alu sequences in particular. We decoupled ADNP and CTCF interplay in our human iPSCs model, and found a global redistribution of active enhancer histone marks signature, which sustain upregulation with the intervention of EZH2-mediated derepression. Finally, HVDAS cortical organoid models show morpho-functional impairment in the early stages of neuronal differentiation, with decreased size and lower mitotic activity, coupled with accelerated maturation phenotype assessed through single-cell transcriptomic analysis. Altogether, with these results we delineate how ADNP deficiency affects pluripotent regulatory landscape and disease-relevant mechanisms that ultimately impact neuronal development and functionality.

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Kanton, Sabina. « Dissecting human cortical development evolution and malformation using organoids and single-cell transcriptomics ». 2019. https://ul.qucosa.de/id/qucosa%3A71686.

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During the last years, important progress has been made in modeling early brain development using 3-dimensional in vitro systems, so-called cerebral organoids. These can be grown from pluripotent stem cells of different species such as our closest living relatives, the chimpanzees and from patients carrying disease mutations that affect brain development. This offers the possibility to study uniquely human features of brain development as well as to identify gene networks altered in neurological diseases. Profiling the transcriptional landscape of cells provides insights into how gene expression programs have changed during evolution and are affected by disease. Previously, studies of this kind were realized using bulk RNA-sequencing, essentially measuring ensemble signals of genes across potentially heterogeneous populations and thus obscured subtle changes with respect to transient cell states or cellular subtypes. However, remarkable advances during the last years have enabled researchers to profile the transcriptomes of single cells in high throughput. This thesis demonstrates how single-cell transcriptomics can be used to dissect human-specific features of the developing and adult brain as well as cellular subpopulations dysregulated in a malformation of the cortex.

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Chapitres de livres sur le sujet "Organoides corticaux"

Schütze, Theresa M., Nora Bölicke, Katrin Sameith et Mareike Albert. « Profiling Cell Type-Specific Gene Regulatory Regions in Human Cortical Organoids ». Dans Neuromethods, 17–41. New York, NY : Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2720-4_2.

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Actes de conférences sur le sujet "Organoides corticaux"

Barton, Shawn, Alexia King, Anson Sing, Maureen Sampson et Steven Sloan. « Elucidating Mechanism of Ammonia Toxicity Using Cortical Organoids (P5-7.001) ». Dans 2023 Annual Meeting Abstracts. Lippincott Williams & Wilkins, 2023. http://dx.doi.org/10.1212/wnl.0000000000202187.

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Wilson, Madison N., Martin Thunemann, Francesca Puppo, Emily Martin, Rebeca Blanch, Fred H. Gage, Alysson R. Muotri, Anna Devor et Duygu Kuzum. « Investigation of functional integration of cortical organoids transplanted in vivo towards future neural prosthetics applications ». Dans 2023 11th International IEEE/EMBS Conference on Neural Engineering (NER). IEEE, 2023. http://dx.doi.org/10.1109/ner52421.2023.10123847.

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