Ptbp1 deletion does not induce glia-to-neuron conversion in adult mouse retina and brain.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE184933 | GEO | 2021/12/07
REPOSITORIES: GEO
Similar Datasets
Project description:Ptbp1 deletion does not induce glia-to-neuron conversion in adult mouse retina and brain.
| PRJNA767059 | ENA
Project description:Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Mϋller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Mϋller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion.
| S-EPMC9619396 | biostudies-literature
Project description:In order to identify the mRNAs in adult light damaged Muller glia of the the neural retina, Müller glia from Hes-5 GFP reporter mice that were crossed with Swiss Webster mice were isolated by means of fluorescent activated cell sorting and analyzed their mRNAs using the Mouse Gene 1.0 ST microarray (Affymetrix). Differentially expressed genes were analyzed and compared to the genes found upregulated in the Dicer-cKO mouse (Wohl at el., 2017). miRNA:mRNA target tools were used to find potential miRNA targets of Muller glia miRNAs.
2020-12-24 | GSE163753 | GEO
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
Project description:In order to identify the miRNAs in adult light damaged Muller glia of the the neural retina, we isolated the Müller glia from Rlbp-CreER: Stopf/f-tdTomato by means of fluorescent activated cell sorting and analyzed their miRNAs using NanoStrings Technologies®. We compared the data to that from and Dicer1-CKO Müller glia and wild type glia Müller glia (GSE103098). We found three miRNAs potentially regulating genes involved in stress response in both data sets.
2020-12-24 | GSE162993 | GEO
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
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:The mammalian central nervous system (CNS) is capable of tolerating chronic hypoxia, but cell type-specific responses to this stress have not been systematically characterized. In the Norrin-knockout (NdpKO) mouse, a model of familial exudative vitreoretinopathy (FEVR), developmental hypovascularization of the retina produces chronic hypoxia of inner nuclear layer (INL) neurons and Muller glia. We have used single-cell RNA sequencing, untargeted metabolomics, and metabolite labeling from 13C-glucose to compare wild type and NdpKO retinas. In NdpKO retinas, we observe gene expression responses consistent with hypoxia in Muller glia and retinal neurons, and we find a metabolic shift that combines reduced flux through the tricarboxylic acid cycle with increased synthesis of serine, glycine, and glutathione. We also used single-cell RNA sequencing to compare the responses of individual cell types in NdpKO retinas to those in the hypoxic cerebral cortex of mice that were housed for one week in a reduced oxygen environment (7.5% oxygen). In the hypoxic cerebral cortex, glial transcriptome responses most closely resemble the response of Muller glia in the NdpKO retina. In both retina and brain, vascular endothelial cells activate a previously dormant tip cell gene expression program, which likely underlies the adaptive neo-angiogenic response to chronic hypoxia. These analyses of retina and brain transcriptomes at single-cell resolution reveal both shared and cell-type-specific changes in gene expression in response to chronic hypoxia, implying both shared and distinct cell type-specific physiologic responses.
2019-04-19 | GSE125708 | GEO
Project description:In this work we identify genes differentially expressed in Muller glia form uninjured and injured retina with and without apobec2a knockdown
2020-05-19 | GSE145330 | GEO
Project description:Loss of neurons in the neural retina is a leading cause of vision loss. Retinal regeneration in zebrafish is attributed to Müller glia, which are activated, adopt a stem cell-like state, proliferate, and generate new neurons. Despite the same endogenous Müller glia being present in all vertebrates including humans, Müller glia activation in mammals leads to glial scarring instead of neurogenesis. Therefore, understanding Müller glia cellular states and molecular processes during zebrafish regeneration may allow us to improve mammalian regeneration. Since only a subset of Müller glia activate following neuron loss, we asked whether a specialised subset of Müller glia might be genetically primed for activation. Single-cell RNA sequencing (sc-RNAseq) from integrated zebrafish Müller glia samples reveals heterogeneity of gene expression across the quiescent Müller glia pool with 4 main clusters emerging, two of which are genetically similar. Labelling for key differentially expressed markers identified that these main clusters correlated with glia spatially distributed across dorsal, central and ventral retina. Using a genetically driven, chemically induced nitroreductase approach, three distinct photoreceptor types were ablated: the long (Lws2), short wavelength-sensitive (Sws2) and rod (Xops) photoreceptors, which also differ in their abundance. As expected, histological analysis of the three injuries and sc-RNAseq data for the two cone photoreceptor ablations identified common genetic program involved in the transition of Müller glia quiescence to activation, and differential responses to injury related to either injury extent or subtype of photoreceptor targeted. Interestingly, despite differences in the distributed across the retina, biased activation of Müller glia was observed in dorsal and central regions. Gene ontology analysis revealed that these injury-responsive dorsal and central Müller glia express genes related to dorsal/ventral pattern formation, growth factor activity, and regulation of developmental process. Müller glia upregulated genes related to homeostasis as well as certain AP-1 and injury-responsive transcription factors, followed by expression of genes involved in cell cycle, chromatin remodeling, and microtubule organisation. Prior to cell cycle entry, Müller glia show a transient upregulation of genes involved in gliogenesis, and Notch signalling. These findings enhance our understanding of heterogeneous states of quiescent Müller glia, and how these differences relate to activation and regeneration potential following neural ablation. A comparison of the distinct quiescent Müller glia with glia states in mammals will reveal key molecular pathways that could be targeted for improved mammalian neural regeneration.
2023-08-21 | GSE218107 | GEO