Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE67899E-GEOD-67898
PROVIDER: PRJNA281448 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1979200.fastq.gz | Fastqsanger.gz | |||
| SRR1979201.fastq.gz | Fastqsanger.gz | |||
| SRR1979202.fastq.gz | Fastqsanger.gz | |||
| SRR1979203.fastq.gz | Fastqsanger.gz | |||
| SRR1979194.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness. Most vision loss occurs following the transition from a disease of deposit formation and inflammation to a disease of neovascular fibrosis and/or cell death. Here, we investigate how repeated wound stimulus leads to seminal changes in gene expression and the onset of a perpetual state of stimulus-independent wound response in retinal pigmented epithelial (RPE) cells, a cell-type central to the etiology of AMD. Using a human fetal RPE cell culture model that considers monolayer disruption and subconfluent culture as a proxy for wound stimulus, we have shown that prolonged wound stimulus leads to terminal acquisition of a mesenchymal phenotype post-confluence and altered expression of more than 40% of the transcriptome (see GEO:GSE62224). In contrast, at subconfluence fewer than 5% of expressed transcripts have 2-fold or greater expression differences after repeated passage. Protein-protein and pathway interaction analysis of the genes with passage-dependent expression levels in subconfluent cultures reveals a 158-node interactome comprised of two interconnected modules with functions pertaining to wound response and cell division. Among the wound response genes are the TGFb pathway activators: TGFB1, TGFB2, INHBA, INHBB, GDF6, CTGF, and THBS1. Significantly, inhibition of TGFBR1/ACVR1B mediated signaling using receptor kinase inhibitors both forestalls and reverses the passage-dependent loss of epithelial potential. In this RNA-Seq based transcriptome analysis we show that the TGFb receptor kinase inhibitor, A-83-01, largely reverses the effects of passage and restores the transcriptome profile of Passage 4 RPE highly similar to that seen in differentiated Passage 0 RPE. Examination of mRNA expression in three different primary fetal RPE donor lines in 32 day old passage 0, passage 3, and passage 3 treated with 500 nM A-83-01 cultures
2015-07-06 | E-GEOD-67898 | biostudies-arrayexpress
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness. Most vision loss occurs following the transition from a disease of deposit formation and inflammation to a disease of neovascular fibrosis and/or cell death. Here, we investigate how repeated wound stimulus leads to seminal changes in gene expression and the onset of a perpetual state of stimulus-independent wound response in retinal pigmented epithelial (RPE) cells, a cell-type central to the etiology of AMD. Using a human fetal RPE cell culture model that considers monolayer disruption and subconfluent culture as a proxy for wound stimulus, we have shown that prolonged wound stimulus leads to terminal acquisition of a mesenchymal phenotype post-confluence and altered expression of more than 40% of the transcriptome (see GEO:GSE62224). In contrast, at subconfluence fewer than 5% of expressed transcripts have 2-fold or greater expression differences after repeated passage. Protein-protein and pathway interaction analysis of the genes with passage-dependent expression levels in subconfluent cultures reveals a 158-node interactome comprised of two interconnected modules with functions pertaining to wound response and cell division. Among the wound response genes are the TGFb pathway activators: TGFB1, TGFB2, INHBA, INHBB, GDF6, CTGF, and THBS1. Significantly, inhibition of TGFBR1/ACVR1B mediated signaling using receptor kinase inhibitors both forestalls and reverses the passage-dependent loss of epithelial potential. In this RNA-Seq based transcriptome analysis we show that the TGFb receptor kinase inhibitor, A-83-01, largely reverses the effects of passage and restores the transcriptome profile of Passage 4 RPE highly similar to that seen in differentiated Passage 0 RPE.
2015-07-06 | GSE67898 | GEO
Project description:TGFbeta-mediated epithelial-to-mesenchymal transition (EMT) is a major component of the wound healing response and a negative determinant of retinal pigment epithelial (RPE) differentiation after periods of sustained sub-confluent culture or repetitive passage. Inhibition of TGFbeta signaling using receptor kinase inhibitors forestalls the onset of passage-dependent EMT and can restore the capacity to differentiate to cells that previously underwent the mesenchymal switch [Radeke et al., 2015, Genome Med. 7:58]. However, even with the sustained inhibition of mesenchymal gene expression using TGFbeta signaling inhibitors the cells eventually lose the capacity to attain a characteristic phenotype. This suggests that there are additional mechanisms at play that contributeto the prevention of RPE differentiation after protracted periods of wound stimulus and mitosis. In this study we investigate the non-TGFbeta-mediated processes that contribute to the demise of the RPE phenotype after extended periods of proliferative wound response. Using comparative transcriptomics, we show that with increasing passage there is a downregulation of RPE genes, misregulation of cell cycle genes, a decline in proliferative potential that cannot be prevented or reversed by inhibition of TGFbeta signaling using the TGFbeta receptor kinase inhibitor A-83-01. Importantly, among the RPE genes with decreased expression are several transcription factors known to be critical for RPE development. Exogenous expression of MYCN and OTX2 in conjunction with A-83-01 treatment restored the ability of passage 7 RPE to differentiate. Taken together, these results demonstrate that the loss of capacity to differentiate as a result of chronic wound stimulus is a product of both TGFbeta pathway-dependent increases in mesenchymal gene expression and a TGFbeta pathway-independent loss of RPE programming.
2016-12-01 | GSE78740 | GEO
Project description:Transcription profiling by high throughput sequencing of human fetal differentiated P0 retinal pigment epithelial cells, mesenchymal P4 cells, and A-83-01 rescued P4 cells
2025-01-17 | E-GEOD-67898 | ExpressionAtlas
Project description:Young mice were compared to old mice (2 month vs 24 month) to determine gene changes that occur with aging in the mouse retinal pigmented epithelium/choroid of the eye. Keywords = retinal pigmented epithelium Keywords = aging Keywords = choroid
2010-06-05 | E-GEOD-565 | biostudies-arrayexpress
Project description:Human neuroblatoma cell lines (N=25) and retinal pigmented epithelium cell lines (N=4) were analyzed for gene expression under untreated/baseline growth conditions. Expression profiling and characterization of a set of Neuroblastoma and retinal pigmented epithelium cell lines
2016-02-19 | E-GEOD-78061 | biostudies-arrayexpress
Project description:Young mice were compared to old mice (2 month vs 24 month) to determine gene changes that occur with aging in the mouse retinal pigmented epithelium/choroid of the eye. Keywords = retinal pigmented epithelium Keywords = aging Keywords = choroid Keywords: other
2003-09-30 | GSE565 | GEO
Project description:To characterize gene expression changes in mice following serous retinal detachments, we employed whole genome microarray expression profiling as a tool to identify genes with the potential effects on the neural retina as well as retinal pigmented epithelium. Total RNA was harvested from nm3342 (mutant) and age-matched wild-type (C57Bl/6J) mice at P30 or P365 for examination using microarray analysis. Retinas and retinal pigmented epithelium was harvested from both age-matched mutant and wild-type mice.
2015-05-16 | E-GEOD-68961 | biostudies-arrayexpress
Project description:Human induced pluripotent stem cells (hiPSCs) can be practically derived from neonatal human epidermal keratinocytes (NHEKs) transduced with OCT4, by a novel cocktail of small molecules including 5 μM PS48, 0.25 mM NaB, 0.5 μM A-83-01 and 0.5 μM PD0325901. These iPSCs are morphologically, molecularly and functionally similar to pluripotent hESCs. NHEKs were cultured in a 100 mm tissue culture dish and transduced 3 times (3-4 hours each transduction) with freshly produced lentivirus supernatants. 1,000,000 transduced NHEKs were seeded on the irradiated x-ray inactivated CF1 MEF feeder cells in a 100-mm dish and cultured in KCM and treated with 5 μM PS48, 0.25 mM NaB (Stemgent) and 0.5 μM A-83-01 (Stemgent) for 2 weeks, followed by changing half volume of media to hESCM and supplementing with 5 μM PS48, 0.25 mM NaB and 0.5 μM A-83-01 for another 2 weeks. Then cell culture media were changed to hESCM and supplemented with 5 μM PS48, 0.25 mM NaB, 0.5 μM A-83-01 and 0.5 μM PD0325901 (Stemgent) for additional four weeks.The culture was split by Accutase (Millipore) and treated with 1 μM Thiazovivin (Stemgent) in the first day after splitting. The iPSC colonies stained positive by Alexa Fluor 555 Mouse anti-Human TRA-1-81 antibody (BD Pharmingen) were picked up for expansion on feeder cells in hESCM and cultured routinely.
2010-12-03 | GSE25218 | GEO