Diversification of multipotential postmitotic mouse retinal Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
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PROVIDER: PRJNA770676 | ENA |
REPOSITORIES: ENA
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Project description:The genesis of broad neuronal classes from multipotential neural progenitor cells has been extensively studied, but less is known about the diversification of a single neuronal class into multiple types. We used single-cell RNA-seq to study how newly-born (postmitotic) mouse retinal ganglion cell (RGC) precursors diversify into ~45 discrete types. Computational analysis provides evidence that RGC type identity is not specified at mitotic exit, but acquired by gradual, asynchronous fate restriction of postmitotic multipotential precursors. Some types are not identifiable until a week after they are generated. Immature RGCs may be specified to project ipsilaterally or contralaterally to the rest of the brain before their type identity has been determined. Optimal transport inference identifies groups of RGC precursors with largely non-overlapping fates, distinguished by selectively expressed transcription factors that could act as fate determinants. Our study provides a framework for investigating the molecular diversification of discrete types within a neuronal class.
2022-02-01 | GSE185671 | GEO
Project description:During retinal development, progenitor cells give rise to six different types of neurons, and one glial cell. This process requires the expression of genes that confer specific functions and identity to each cell. Previous works have reported the miRNAs expression profile in retina, but is still necessary to further define individual retinal cell populations profiles. We isolated postmitotic mice CD73-positive Rods, Müller glial cells and Retinal Progenitors Cells (E17.5); we then analyzed their miRNA profile expression by microarrays. Using wild type mice we FACS-isolated postmitotic CD73-positive Rods (posnatal day 5). We isolated primary Müller glia cultures from postnatal day 8 mice and retinal progenitors cells from E17.5 mouse embryos; we then sent the samples to the gene expression unit at Instituto de Medicina Genomica (INMEGEN), to analyze their miRNA profile expression by microarrays.
2016-02-09 | E-GEOD-62109 | biostudies-arrayexpress
Project description:Retinal microvascularization can provide important informations to systemic vascular phenomena. The non-invasive quantitative description of the retinal vascularization is now possible by performing OCT-angiography and their image analysis software (vascular density and retinal perfusion). Systemic microvacular changes during the establishment of oncological treatment by targeted antiangiogenic therapy are little described in the literature. The objective of this pilot study is to describe the evolution of the retinal vascular density of patients with antiangiogenic drugs. In addition, the evolution of the retinal vascular density of patients on antiangiogenic drugs will study as a function of the response to the treatment and the toxicity of these treatments.
| 2382594 | ecrin-mdr-crc
Project description:During retinal development, progenitor cells give rise to six different types of neurons, and one glial cell. This process requires the expression of genes that confer specific functions and identity to each cell. Previous works have reported the miRNAs expression profile in retina, but is still necessary to further define individual retinal cell populations profiles. We isolated postmitotic mice CD73-positive Rods, Müller glial cells and Retinal Progenitors Cells (E17.5); we then analyzed their miRNA profile expression by microarrays.
2016-02-09 | GSE62109 | GEO
Project description:Assembly of transcriptomes encoding unique neuronal identities requires selective accessibility of transcription factors to cis-regulatory sequences in nucleosome-embedded postmitotic chromatin. Yet, the mechanisms controlling postmitotic neuronal chromatin accessibility are poorly understood. Here, we show that unique distal enhancers define the Pet1 neuron lineage that generates serotonin (5-HT) neurons. Heterogeneous single cell chromatin landscapes are established early in postmitotic Pet1 neurons and reveal the putative regulatory programs driving Pet1 neuron subtype identities. Distal enhancer accessibility is highly dynamic as Pet1 neurons mature, suggesting the existence of regulatory factors that reorganize postmitotic neuronal chromatin. We find that Pet1 and Lmx1b control chromatin accessibility to select Pet1-lineage specific enhancers for 5-HT neurotransmission. Additionally, these factors are required to maintain chromatin accessibility during early maturation suggesting that postmitotic neuronal open chromatin is unstable and requires continuous regulatory input. Together our findings reveal postmitotic transcription factors that reorganize accessible chromatin for neuron specialization.
2022-04-14 | GSE185737 | GEO
Project description:Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons. Mouse E14.5 neocortices and Postnatal day (P) 0.5 brains: E14.5 neocortices KO, 3; E14.5 neocortices WT, 3; Postnatal day (P) 0.5 brains frontal WT, 4; Postnatal day (P) 0.5 brains frontal KO, 4; Postnatal day (P) 0.5 brains parietal WT, 4; Postnatal day (P) 0.5 brains parietal KO, 4; Postnatal day (P) 0.5 brains occipital WT, 4; Postnatal day (P) 0.5 brains occipital KO, 4.
2010-07-27 | E-GEOD-22371 | biostudies-arrayexpress
Project description:ES/iPS-retinal sheet transplantation, which supplies photoreceptors as well as other retinal cells, has been shown able to restore visual function in mice with end-stage retinal degeneration. Here, we introduce a novel type of genetically engineered mouse ES/iPS-retinal sheet with reduced numbers of secondary retinal neurons but intact photoreceptor cell layer structure (Bhlhb4 knockout and Islet1 knockout). We show that this KO grafts can differentiate into retinal organoids with similar potency as wildtype retinal organoids. The data set contains data from 3 cell lines: wildtype (WT, specified as ‘NCT’), B4KO (Bhlhb4 knock-out), and Isl1KO(Islet-1 knockout) across 3 differential days (DDs, DD10, DD16, and DD23) along the early differentiation of retinal tissue.
2021-06-23 | GSE178653 | GEO
Project description:TP53 is the most frequently mutated gene in human cancers, and despite intensive research efforts, genome-scale studies of p53 function in whole animal models are rare. Yet the need for such in vivo studies is underscored by recent challenges to established models indicating that unappreciated p53 functions contribute to tumor suppression. Here we leveraged the Drosophila system to interrogate p53 function in a postmitotic context. In the developing fly, p53 robustly activates important apoptotic genes in response to radiation-induced DNA damage. We have recently shown that a p53 enhancer near the cell death gene reaper (p53RErpr), forms chromatin contacts and enables p53 target activation through long genomic distances. Interestingly, we found that this canonical p53 apoptotic program fails to activate in response to radiation in postmitotic tissue. Furthermore, the lack of apoptotic responses was not associated with altered chromatin contacts; instead we determined that p53 does not occupy the p53RErpr enhancer in postmitotic tissue. In addition, we conducted RNA-seq and ChIP-seq studies to directly compare the developing and postmitotic tissues, and we determined that p53 regulates distinct transcriptional programs in adult heads, which include DNA repair, metabolism and proteolysis genes. Strikingly, in the postmitotic context p53 binding landscapes were poorly correlated with nearby transcriptional effects, raising the possibility that p53 enhancers could be generally acting through long distances.
2019-07-15 | GSE109292 | GEO
Project description:The goal of the project is to identify novel therapeutic targets for retinal vascular hyperpermeability. Three condition (Control, VEGF, and Anti-VEGF) sample of mouse retinal tissues were extensively characterized by global proteome profiling.
2016-03-22 | PXD003656 | Pride
Project description:Loss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling. We used microarrays to examine gene expression changes that occur in single cells after the removal of Notch1 during retinal development.
2013-09-06 | GSE35682 | GEO