Mammalian Müller glia Fate Determination between Gliosis and Reprogramming
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Zuguo Liu
PROVIDER: PXD072785 | iProX | Wed Jan 07 00:00:00 GMT 2026
REPOSITORIES: iProX
Similar Datasets
Project description:Irreversible loss of retinal neurons is the leading cause of blindness. Harnessing the latent stem cell potential of mammalian Müller glia offers a promising strategy for endogenous retinal regeneration. Shifting the Müller glia response from gliosis to regeneration after retinal injury is a critical step in promoting the orderly entry of Müller glia into a regenerative program. However, the molecular switch governing this divergent fate decision remains elusive. Here, through RNA-seq and scRNA-seq, we confirm the upstream determinant of Müller glia fate after retinal injury.
2026-01-18 | GSE316279 | GEO
Project description:Irreversible loss of retinal neurons is the leading cause of blindness. Harnessing the latent stem cell potential of mammalian Müller glia offers a promising strategy for endogenous retinal regeneration. Shifting the Müller glia response from gliosis to regeneration after retinal injury is a critical step in promoting the orderly entry of Müller glia into a regenerative program. However, the molecular switch governing this divergent fate decision remains elusive. Here, through RNA-seq and scRNA-seq, we confirm the upstream determinant of Müller glia fate after retinal injury.
2026-01-18 | GSE316280 | GEO
Project description:MAPK14 Governs Mammalian Müller glia Fate Determination between Gliosis and Reprogramming
| PRJNA1402154 | ENA
Project description:Regeneration of neurons has enormous implications for human health and is a topic of interest both from the biological and translational perspective. The retina poses an excellent system to study the potential of replacing neurons following injury and the impact different lesions can have on this process. We have established mouse models where proneural transcription factors are expressed in Müller glia to stimulate neurogenesis, which is analogous to how zebrafish regenerate the retina after injury. Our previous studies have shown that Müller glia overexpressing either Ascl1 or Ascl1-Atoh1 will respond to inner retinal damage, caused by a neurotoxic dose of NMDA, by acquiring a progenitor-like state and giving rise to bipolar cells or retinal ganglion-like cells, respectively. It was not known however whether neurogenesis would still occur if the retina suffered outer retinal injury and if the timing of injury relative to the expression of proneural factors was critical for the process. To address these questions, we explored whether timing or mode of injury affect the induced neurogenesis from MG. We show that reprogramming MG with Ascl1 is not impacted by the mode or timing of injury, since all paradigms resulted in similar ratios of new bipolar neurons. By contrast, MG that express Ascl1-Atoh1 respond to outer retinal damage by producing a new type of retinal ganglion-like cell that is not generated after NMDA injury. Therefore, although the fate of reprogrammed neurons is mostly dictated by the proneural transcription factors, there is a context-dependent effect of the injured retinal microenvironment.
2023-12-13 | GSE250019 | GEO
Project description:MAPK14 Governs Mammalian Müller glia Fate Determination between Gliosis and Reprogramming [scRNA-Seq]
| PRJNA1402153 | ENA
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
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
Project description:Fibroblasts can be reprogrammed into induced cardiomyocyte-like cells (iCMs) by forced expression of cardiogenic transcription factors. However, it remains unknown how fibroblasts adopt a cardiomyocyte (CM) fate during their spontaneous ongoing transdifferentiation toward myofibroblasts (MFs). By tracing fibroblast lineages following cardiac reprogramming in vitro, we found that most mature iCMs are derived directly from fibroblasts without transition through the MF state. This direct conversion is attributable to mutually exclusive induction of cardiac sarcomeres and MF cytoskeletal structures in the cytoplasm of fibroblasts during reprogramming. For direct fate switch from fibroblasts to iCMs, significant remodeling of actin isoforms occurs in fibroblasts, including induction of α-cardiac actin and decrease of the actin isoforms predominant in MFs. Accordingly, genetic or pharmacological ablation of MF-enriched actin isoforms significantly enhances cardiac reprogramming. Our results demonstrate that remodeling of actin isoforms is required for fibroblast to CM fate conversion by cardiac reprogramming.
| S-EPMC9287671 | biostudies-literature
Project description:The study was aimed at comparing the transcriptome of MG cells of the retina with the progenitors derived from them after an injury. This information will help in the identification of factors that are responsible for the retinal regeneration. Muller glia were isolated by fluorescent activated cell sorting (FACS) using uninjured retinas from transgenice zebrafish (gfap:gfp) where green florescent protein (GFP) is under the control of the glial fibrillary acidic protein (gfap) promoter. MG-derived retinal progenitors were isolated by FACS at 4 days post retinal injury from 1016 tuba1a:gfp transgenic fish where GFP is driven by the tuba1a promoter which is specifically activated in these progenitors. Total RNA was isolated from these cell populations and subjected to microarray analysis to compare their transcriptomes. Samples were prepared in duplicate.
2012-08-09 | E-GEOD-36191 | biostudies-arrayexpress
Project description:Retinal damage triggers reactive gliosis in Müller glia across vertebrate species, but only in regenerative animals, such as teleost fish, do Müller glia initiate repair; proliferating and undergoing neurogenesis to replace lost cells. We found that Plagl1, a maternally imprinted gene, is dynamically regulated in reactive Müller glia post-insult, with transcript levels transiently increasing before stably declining. To study Plagl1 retinal function, we examined Plagl1+/-pat null mutants postnatally, revealing defects in retinal architecture, visual signal processing and a reactive gliotic phenotype. Plagl1+/-pat Müller glia proliferate ectopically and give rise to inner retinal neurons and photoreceptors. Transcriptomic and ATAC-seq profiles revealed similarities between Plagl1+/-pat retinas and neurodegenerative and injury models, including an upregulation of pro-gliogenic and pro-proliferative pathways, such as Notch, not observed in wild-type retinas Plagl1 is thus an essential component of the transcriptional regulatory networks that retain mammalian Müller glia in quiescence.
2021-05-06 | GSE173942 | GEO