Ngn3 reprograms late retinal progenitor cells through transcriptional and epigenetic mechnisms [ATAC-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE326388 | GEO | 2026/04/24
REPOSITORIES: GEO
Similar Datasets
Project description:Ngn family transcription factors exhibit potent capacity to promote neurogenesis under diverse cellular context. Using in vivo electroporation on newbone mouse pups retinas, we demonstrate that overexpression of Ngn3 (Ngn3-OE) reprogramms the differentiation competent status of late retinal progenitor celle (RPC), promoting rod photoreceptor differentiation while repressing the fates of Müller glial cell and other interneurons. Herein, we perform RNA-seq and ATAC-seq to investigate the underlying molecular mechanism by which Ngn3 reprogramms late RPCs.
2026-04-24 | GSE326387 | GEO
Project description:microRNAs (miRNAs) play a pivotal role during the early phases of retinal development, but their impact on late-phase retinogenesis is unknown. We depleted miRNAs in late retinal progenitor/precursor cells (RPCs/PCs) via a conditional Dicer knock-out. Optical coherence tomography (OCT), electroretinography (ERG), histological, and transcriptional analyses were conducted in young and adult mice. Alterations in gene expression of late-born cells were observed as early as postnatal day 7 (P7), resulting in impaired rod function, a significantly reduced number of rod bipolar cells and their associated function, and a decreased Müller glia population at adult age. These defects appear to be caused by a delay in differentiation/ incomplete maturation, as indicated by an enlarged progenitor/precursor population at young ages that persists into adulthood. Notably, an increased population of HuC/D+ amacrine cells was found. Luciferase assays led us to speculate that this increase may be due to the absence of Elavl3 suppression via RPC-miRNAs. This suggests that Dicer/miRNAs in late RPC/PCs are essential for the proper formation and maturation of late RPC progenies and may also play a role in regulating cell state.
2025-09-18 | GSE288381 | GEO
Project description:Dynamic epigenetic changes guide retinal progenitor cells (RPCs) toward diverse neuronal subtypes and Müller glia during retinal development. However, the epigenetic mechanisms that maintain RPC proliferative and neurogenic potential throughout the final stages of retinal cell genesis remain poorly understood. Here, we integrate RNA sequencing and assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate how mouse RPC stemness is regulated. Our analysis reveals conserved chromatin accessibility and gene expression profiles in mouse RPCs throughout retinal cell genesis. Notably, the histone methyltransferase Setd8, which catalyzes H4K20 monomethylation, remains persistently expressed in RPCs but is barely detectable in adult Müller glia. Setd8 deletion in developing RPCs reduces proliferation, triggers apoptosis, and disrupts retinal laminar organization and ocular axis length. Additionally, Setd8 deficiency impairs the chromatin accessibility that is normally preserved in RPCs, leading to a partial acquisition of a transcriptomic profile associated with terminally differentiated cells. Our study indicates that Setd8 safeguards mouse RPC identity by maintaining RPC-specific chromatin accessibility, thereby ensuring proper retinal development.
2026-01-13 | GSE303990 | GEO
Project description:Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expression profiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix-loop-helix (bHLH) transcription factor, Olig2. In contrast to the large and complex set of clones generated by viral marking of random embryonic RPCs, the embryonic Olig2+ RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time. The embryonically produced cell types made by Olig2+ RPCs were cone photoreceptors and horizontal cell (HC) interneurons. Moreover, the embryonic Olig2+ RPC did not make the later Olig2+ RPC. The later, postnatal Olig2+ RPCs also made terminal divisions, which were biased towards production of rod photoreceptors and amacrine cell (AC) interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases towards producing subsets of retinal neurons in a terminal division, with the types of neurons produced varying over time. This strategy is similar to that of the developing Drosophila melanogaster ventral nerve cord, with the Olig2+ cells behaving as ganglion mother cells. Single retinal cells were isolated in tubes containing lysis buffer, their mRNAs were reverse transcribed, and the resulting cDNAs were PCR amplified for 35 cycles. Labeled cDNA samples were hybridized to Affymetrix 430 2.0 microarrays and the data was normalized using MAS5.0 software. These cells were examined for the expression of Olig2 or other bHLH factors.
2012-04-12 | E-GEOD-37207 | biostudies-arrayexpress
Project description:Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expression profiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix-loop-helix (bHLH) transcription factor, Olig2. In contrast to the large and complex set of clones generated by viral marking of random embryonic RPCs, the embryonic Olig2+ RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time. The embryonically produced cell types made by Olig2+ RPCs were cone photoreceptors and horizontal cell (HC) interneurons. Moreover, the embryonic Olig2+ RPC did not make the later Olig2+ RPC. The later, postnatal Olig2+ RPCs also made terminal divisions, which were biased towards production of rod photoreceptors and amacrine cell (AC) interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases towards producing subsets of retinal neurons in a terminal division, with the types of neurons produced varying over time. This strategy is similar to that of the developing Drosophila melanogaster ventral nerve cord, with the Olig2+ cells behaving as ganglion mother cells.
2012-04-13 | GSE37207 | GEO
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. Retinas of Notch1fl/fl P0 pups were electroporated in vivo with plamids encoding Cre driven by a broadly active promoter, CAG, along with a Cre-responsive GFP reporter, also driven by CAG promoter (CALNL-GFP). For controls, the retinas of sibling Notch1fl/fl pups were electroporated with CAG:GFP. The animals were sacrificed at P3 to allow time for Notch1 to be genetically removed and downstream gene expression changes to occur. Retinas electroporated with either CAG;Cre and CALNL-GFP or CAG:GFP alone were dissected and dissociated to individual cells, which were harvested under a dissecting microscope on the basis of their GFP signal.
2013-09-06 | E-GEOD-35682 | biostudies-arrayexpress
Project description:NGN3 is a transcription factor whose transient expression during pancreatic development is vital for the generation of endocrine pancreatic cells, including beta cells. NGN3 stabilisation has been shown to induce exocrine-to-endocrine cell plasticity in the murine pancreas, making it a viable target for therapies aiming to replenish beta cells after immune-mediated destruction in type 1 diabetes patients. Here, we set out to identify new interactors of NGN3 that could play a role in its post-translational regulation. We transfected HEK293A cells with HA-tagged NGN3 and carried out immunoprecipitation of the HA-tag, followed by analysis of co-immunoprecipitated interactors via LC-MS/MS.
2023-03-27 | PXD033691 | Pride
Project description:Ngn family transcription factors (TFs) are important neurogenic regulators during development. The aim of this study is to examine the ability of two Ngn family members, Ngn1 and Ngn3, to induce neuron fates from mouse embryonic fibroblasts (MEFs) through direct cell fate reprogramming.
2024-12-01 | GSE234613 | GEO
Project description:Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. In order to better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profile of differentiating murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An ESC line was created that allows for the induction of Ngn3 by adding doxycycline (Dox) to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of both undifferentiated and differentiated conditions. Characterization of pancreatic developmental markers during embryoid body (EB) formation revealed an optimum context for Ngn3 induction. Neuroendocrine genes including neurogenic differentiation 1 (NeuroD1) and single minded 1 (Sim1) were found to be significantly upregulated. Genes regulated by Ngn3 independent of the context were analyzed using systematic gene ontology tools and revealed Notch signaling as the most significantly regulated signaling pathway (p=0.009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p<0.0001). Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin transcription. Keywords: Ngn3 induction, embryonic stem cell differentiation
2006-07-01 | GSE3653 | GEO
Project description:In order to identify the miRNAs in postnatal day 2 (P2) retinal progenitor cells (RPCs), and P8, P11, and adult Müller glia (MG) of the neural retina, we isolated the retinal progenitors from Sox2-CreER: Stopf/f-tdTomato and MG from Rlbp-CreER: Stopf/f-tdTomato mice by means of fluorescent activated cell sorting and analyzed their miRNAs using NanoStrings Technologies®. We next compared miRNA expression of RPCs with MG. We found that most specific miRNAs decline with glial maturation (RPC miRNAs) while others increase (MG miRNAs). Overexpression of miRNA-25 found in RPCs and inhibition of MG miRNA let-7 can induce a neurogenic potential in MG and initiates a de novo differentiation toward neuronal fates.
2019-08-14 | GSE135835 | GEO