Drop-Seq analysis of P17 FACS sorted retinal cells from the Tg(Chx10-EGFP/cre,-ALPP)2Clc or Vsx2-GFP transgenic line
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81904 | GEO | 2016/08/25
SECONDARY ACCESSION(S): PRJNA323370
REPOSITORIES: GEO
Similar Datasets
Project description:Vsx2-GFP mouse retinas were dissected, FACS sorted for GFP+ cells and single-cell mRNAseq libraries generated with Drop-Seq Drop-Seq was performed on two different batches. Bipolar1-Bipolar4 are replicates from batch 1 and Bipolar5-6 are replicates from Batch 2
2016-08-25 | E-GEOD-81904 | biostudies-arrayexpress
Project description:Three Vsx2-GFP mouse retinas were dissected, dissociated and FACS sorted, and single cell RNA-seq libraries were generated for 288 single cells and 3 bulk libraries using Smart-seq2 (~10,000 cells each)
2016-08-25 | GSE80232 | GEO
Project description:The roles of retinal cis-regulatory landscape in controlling the expression of gene regulatory networks important for retinogenesis remain poorly understood. Vsx2 is a transcription factor essential for retinal proliferation and bipolar cell differentiation but the molecular mechanisms underlying its developmental roles are unclear. Here, we profiled VSX2 genomic occupancy during mouse retinogenesis, revealing extensive retinal gene regulatory networks associated with Vsx2 during development. We defined an autoregulatory loop in which VSX2 binds and transactivates its own enhancer in association with the transcription factor PAX6 . The Vsx2 regulatory landscape contains elements that are required for Vsx2 expression, retinal proliferation and proper cell type differentiation. We further show that retinae in which the Vsx2 enhancer landscape has been largely deleted suffer a bias toward photoreceptor production. Genomic data indicate that VSX2 occupies cis-regulatory elements nearby genes associated with photoreceptor differentiation and homeostasis in mouse and human retinae, including a conserved region nearby the rod-specifying factor Prdm1. We provide evidence that VSX2 associates with OTX2 and can act to suppress OTX2-dependent enhancer transactivation of Prdm1 enhancer. Taken together, our analyses illuminate important mechanistic insights on how VSX2 is engaged with gene regulatory networks that are essential for retinal proliferation and cell fate acquisition.
2022-07-13 | GSE196104 | GEO
Project description:The roles of retinal cis-regulatory landscape in controlling the expression of gene regulatory networks important for retinogenesis remain poorly understood. Vsx2 is a transcription factor essential for retinal proliferation and bipolar cell differentiation but the molecular mechanisms underlying its developmental roles are unclear. Here, we profiled VSX2 genomic occupancy during mouse retinogenesis, revealing extensive retinal gene regulatory networks associated with Vsx2 during development. We defined an autoregulatory loop in which VSX2 binds and transactivates its own enhancer in association with the transcription factor PAX6 . The Vsx2 regulatory landscape contains elements that are required for Vsx2 expression, retinal proliferation and proper cell type differentiation. We further show that retinae in which the Vsx2 enhancer landscape has been largely deleted suffer a bias toward photoreceptor production. Genomic data indicate that VSX2 occupies cis-regulatory elements nearby genes associated with photoreceptor differentiation and homeostasis in mouse and human retinae, including a conserved region nearby the rod-specifying factor Prdm1. We provide evidence that VSX2 associates with OTX2 and can act to suppress OTX2-dependent enhancer transactivation of Prdm1 enhancer. Taken together, our analyses illuminate important mechanistic insights on how VSX2 is engaged with gene regulatory networks that are essential for retinal proliferation and cell fate acquisition.
2022-07-13 | GSE196103 | GEO
Project description:The roles of retinal cis-regulatory landscape in controlling the expression of gene regulatory networks important for retinogenesis remain poorly understood. Vsx2 is a transcription factor essential for retinal proliferation and bipolar cell differentiation but the molecular mechanisms underlying its developmental roles are unclear. Here, we profiled VSX2 genomic occupancy during mouse retinogenesis, revealing extensive retinal gene regulatory networks associated with Vsx2 during development. We defined an autoregulatory loop in which VSX2 binds and transactivates its own enhancer in association with the transcription factor PAX6 . The Vsx2 regulatory landscape contains elements that are required for Vsx2 expression, retinal proliferation and proper cell type differentiation. We further show that retinae in which the Vsx2 enhancer landscape has been largely deleted suffer a bias toward photoreceptor production. Genomic data indicate that VSX2 occupies cis-regulatory elements nearby genes associated with photoreceptor differentiation and homeostasis in mouse and human retinae, including a conserved region nearby the rod-specifying factor Prdm1. We provide evidence that VSX2 associates with OTX2 and can act to suppress OTX2-dependent enhancer transactivation of Prdm1 enhancer. Taken together, our analyses illuminate important mechanistic insights on how VSX2 is engaged with gene regulatory networks that are essential for retinal proliferation and cell fate acquisition.
2022-07-13 | GSE196097 | GEO
Project description:Rod-derived Cone Viability Factor (RdCVF) is a trophic factor with therapeutic potential for the treatment of retinitis pigmentosa, a retinal disease that commonly results in blindness. RdCVF is encoded by Nucleoredoxin-like 1 (Nxnl1), a gene homologous with the family of thioredoxins that participate in the defense against oxidative stress. RdCVF expression is lost after rod degeneration in the first phase of retinitis pigmentosa, and this loss has been implicated in the more clinically significant secondary cone degeneration that often occurs. Here, we describe a study of the Nxnl1 promoter using an approach that combines promoter and transcriptomic analysis. By transfection of selected candidate transcription factors, chosen based upon their expression pattern, we identified the homeodomain proteins CHX10/VSX2, VSX1 and PAX4, as well as the zinc finger protein SP3, as factors that can stimulate both the mouse and human Nxnl1 promoter. In addition, CHX10/VSX2 binds to the Nxnl1 promoter in vivo. Since CHX10/VSX2 is expressed predominantly in the inner retina, this finding motivated us to demonstrate that RdCVF is expressed in the inner as well as the outer retina. Interestingly, the loss of rods in the rd1 mouse, a model of retinitis pigmentosa, is associated with decreased expression of RdCVF by inner retinal cells as well as by rods. Based upon these results, we propose an alternative therapeutic strategy aimed at recapitulating RdCVF expression in the inner retina, where cell loss is not significant, to prevent secondary cone death and central vision loss in patients suffering from retinitis pigmentosa.
| S-EPMC2796890 | biostudies-literature
Project description:Vertebrate retinal progenitor cells (RPCs) undergo a robust proliferative expansion to produce enough cells for the retina to form appropriately. Vsx2 (formerly Chx10), a homeodomain protein expressed in RPCs, is required for sufficient proliferation to occur. Sonic Hedgehog protein (SHH), secreted by retinal ganglion cells (RGCs), activates Hedgehog (Hh) signaling in RPCs and is also required for sufficient proliferation to occur. Therefore, we sought to determine if reduced Hh signaling is a contributing factor to the proliferation changes that occur in the absence of Vsx2. To do this, we examined Shh expression and Hh signaling activity in the homozygous ocular retardation J (orJ) mouse, which harbors a recessive null allele in the Vsx2 gene. We found that Shh expression and Hh signaling activity are delayed during early retinal development in orJ mice and this correlates with a delay in the onset of RGC differentiation. At birth, reduced expression of genes regulated by Hh signaling was observed despite the production of SHH ligand. orJ RPCs respond to pre-processed recombinant SHH ligand (SHH-N) in explant culture as evidenced by increased proliferation and expression of Hh target genes. Interestingly, proliferation in the orJ retina is further inhibited by cyclopamine, an antagonist of Hh signaling. Our results suggest that reduced Hh signaling contributes to the reduced level of RPC proliferation in the orJ retina, thereby revealing a role for Vsx2 in mediating mitogen signaling.
| S-EPMC2671289 | biostudies-literature
Project description:Functional analysis of Vsx2 super-enhancer reveals an autoregulatory network governing Vsx2 expression during retinogenesis
| PRJNA803274 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. The Vsx2 homeobox gene is expressed in the newly formed retinal domain during early eye development and mutations in the Vsx2 gene cause congenital microphthalmia. The primary disruptions in the early retina are compromised retinal identity (lineage infidelity), reduced proliferation, and delayed neurogenesis. One goal of the study was to use gene expression profiling to predict genetic interactions between Vsx2 and candidate functional interactors that contribute to the early retinal phenotype of the Vsx2-null mouse strain ocular retardation J (orJ). The orJ allele is a spontaneous, recessive allele caused by the presence of a premature stop codon in the Vsx2 homeodomain. The datasets contained within are from three independent experimental designs. One was to compare the retinal gene expression profiles from E12.5 embryos that are one of three genotypes: the orJ-homozygous mutant, the combinatorial orJ; Mitfmi heterozygous mutant, and the orJ-heterozygous mouse (control). Another analysis was to compare the gene expression profiles of E12.5 orJ-homozygous mutant retinal tissues cultured for 24 hour in the presence or absence of the RXR antagonist HX531. The other analysis was to compare the gene expression profiles of E12.5 orJ-homozygous mutant retinal tissues cultured for 24 hour in the presence or absence of the gamma-Secretase antagonist Dibenzazipine (DBZ).
2023-05-19 | GSE227056 | GEO
Project description:A bead supsension and a solution of ERCC spike-ins at a concentration of ~100,000 molecules per droplet was used in Drop-Seq, a novel technology for high-throughput single cell mRNAseq An estimated 84 beads were selected for amplification.
2015-05-20 | E-GEOD-66694 | biostudies-arrayexpress