Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparative transcriptomic and epigenomic analysis identifies key regulators of injury response and neurogenic competence in retinal glia

ABSTRACT: Injury induces retinal Muller glia of non-mammalian, but not mammalian, vertebrates to generate neurons. To identify gene regulatory networks that control neurogenic competence in retinal glia, we used bulk and single-cell RNA-seq and ATAC-seq analysis to comprehensively profile gene expression and chromatin conformation in Muller glia from zebrafish, chick and mice. This was conducted during glial development, following inner and outer retinal injury, as well as following treatment with extrinsic factors that induce glial reprogramming. Integration of these data, together with functional analysis of candidate genes, identified evolutionarily conserved and species-specific gene regulatory networks controlling glial quiescence, gliosis, and neurogenic competence. In zebrafish and chick, transition from quiescence to gliosis is a necessary stage in acquisition of neurogenic competence, while in mice a dedicated network suppresses this transition and rapidly restores quiescence. These findings may help guide the design of cell-based therapies aimed at restoring retinal neurons lost to disease.

ORGANISM(S): Mus musculus Danio rerio

PROVIDER: GSE135406 | GEO | 2020/05/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression data from adult mouse normal and damaged retina from B6 and 129 mouse strains

Project description:Retinal damage causes proliferation of Muller glia, but the degree of proliferation depends on mouse strains. Muller glial proliferation was significantly promoted by the addition of GSK3 inhibitor in 129, but not in B6. We used retinal explant culture as a model for retinal damage which caused preferential photoreceptor death in a few days. We used microarrays to detail the global programme of gene expression regulating the proliferative potential of Muller glia after retinal damage. Total RNA from intact whole retina, retinal tissue cultured for three days, and retinal tissue cultured with chir99021 for three days was used. Retinal tissues from 10 weeks old mice were used.

2014-03-06 | E-GEOD-54056 | biostudies-arrayexpress

Expression data from adult mouse normal and damaged retina from B6 and 129 mouse strains

2014-03-06 | GSE54056 | GEO

Expression profiling of Ascl1-reprogrammed P12 Müller glia compared with freshly dissociated progenitors and Müller glia

Project description:Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia cells (MG) that activate the proneural factor Achaete-scute homolog 1 (Ascl1/Mash1) and de-differentiate into progenitors cells. In contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether Ascl1 could restore a neurogenic potential to mammalian MG, we over-expressed Ascl1 in dissociated mouse MG cultures and intact retinal explants. Ascl1-infected MG upregulate retinal progenitor-specific genes, while downregulating glial genes. Furthermore, Ascl1 remodeled the chromatin at its targets from a repressive to active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers, and displayed neuron-like physiological responses. These results indicate that a single transcription factor, Ascl1, can produce a neurogenic state in mature Muller glia. Expresssion profiling was used to determine the genes that were changed after Ascl1 infection of P12 cultured Müller glia compared with those present in P0 progenitors and P7-P21 Müller glia Retinas were dissociated and FAC-sorted from Hes5-GFP mice at P0, P7, P10, P14 or P21 and submitted for profiling. WT Retinas were dissociated at P12, grown for 1 week in culture, and infected with lentiviruses expressing Ascl1 or GFP for four days. Total RNA was extracted and submitted for profiling.

2013-04-06 | E-GEOD-45835 | biostudies-arrayexpress

GENE EXPRESSION CHANGES WITHIN MM-CM-^\LLER GLIAL CELLS DURING RETINITIS PIGMENTOSA

Project description:Retinitis Pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the MM-CM-<ller glia, play in the progression of the disease. Here we define gene expression changes in MM-CM-<ller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knock-out (Rhod-ko) models. The RNA repertoire of 28 single MGCs was comprehensively profiled, and a comparison was made between MGC from wild type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. MGCs have been shown to respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of GFAP. In this data, many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune related response. It is noteworthy that a high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells, and/or inherent heterogeneity among MGCs. Retinas were dissociated and single Muller Glial Cells were picked under a dissecting microscope using a micropipette based on their distinct morphological shape. Single cell cDNAs were generated and genome wide profiles were obtained by hybridization to Affymetrix 430 2.0 microarrays. Data was normalized using MAS5.0 software. A total of 28 Muller Glial Cells were analyzed and confirmed post hoc by expression of known marker genes.

2014-10-31 | E-GEOD-35386 | biostudies-arrayexpress

Differential expression in Muller glia of injured zebrafish in a mycb-/- context

Project description:This experiment studies retinal regeneration using a zebrafish model with a focus on Muller glia reprogramming.

2024-05-10 | GSE249116 | GEO

Differential expression in Muller glia of injured zebrafish in a mych-/- context

Project description:This experiment studies retinal regeneration using a zebrafish model with a focus on Muller glia reprogramming.

2024-05-10 | GSE249115 | GEO

Expression profiling of Ascl1-reprogrammed P12 Müller glia compared with freshly dissociated progenitors and Müller glia

2013-04-06 | GSE45835 | GEO

Single cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration

Project description:In the lesioned zebrafish retina, Müller glia produce multipotent retinal progenitors that generate all retinal neurons, replacing lost cell types. To study the molecular mechanisms linking Müller glia reactivity to progenitor production and neuronal differentiation, we used single cell RNA sequencing of Müller glia, progenitors and regenerated progeny from uninjured and light-lesioned retinae. We discover an injury-induced Müller glia differentiation trajectory that leads into a cell population with a hybrid identity expressing marker genes of Müller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. We further observe that neurogenic progenitors progressively differentiate to generate retinal ganglion cells first and bipolar cells last, similar to the events observed during retinal development. Our work provides a comprehensive description of Müller glia and progenitor transcriptional changes and fate decisions in the regenerating retina, which are key to tailor cell differentiation and replacement therapies for retinal dystrophies in humans.

2023-03-03 | GSE226373 | GEO

Rapid, dynamic activation of Müller glial stem cell responses in zebrafish

Project description:Purpose: Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases. Methods: To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute, photic lesion, prior to the asymmetric division that produces retinal progenitors. Results: We report a rapid, dynamic response of zebrafish Müller glia, characterized by activation of pathways related to stress, NF-kappa B signaling, cytokine signaling, immunity, prostaglandin metabolism, circadian rhythm, and pluripotency, and an initial repression of Wnt signaling. When we compared publicly available transcriptomes of isolated mouse Müller glia from two retinal degeneration models, we found that mouse Müller glia showed evidence of oxidative stress, variable responses associated with immune regulation, and repression of pathways associated with pluripotency, development, and proliferation. Conclusions: Categories of biological processes/pathways activated following photoreceptor loss in regeneration-competent zebrafish Müller glia, which distinguished them from mouse Müller glia in retinal degeneration models, included: cytokine signaling (notably NF-kappa B), prostaglandin E2 synthesis, expression of core clock genes, and pathways/metabolic states associated with pluripotency. These regulatory mechanisms are relatively unexplored as potential mediators of stem cell properties likely to be important in Müller glial cells for successful retinal regeneration.

2016-09-14 | GSE86872 | GEO

RNA-seq to investigate the adult mouse Muller glia transcriptome

Project description:These data serve as a reference transcriptomic profile for adult mouse retinal Muller glia. Retinas were dissociated into single cell suspensions and sorted into two fractions: a Muller glia-enriched fraction on the basis of Muller glia-specific tdTomato expression and a second fraction containing the remaining retinal cells that were tdTomato-negative. Both fractions were sequenced.

2020-08-02 | E-MTAB-7058 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data