Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE67899E-GEOD-67898
PROVIDER: PRJNA263500 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Retinal Pigment Epithelial (RPE) cells are located behind the retina and are critical for photoreceptor survival. Loss of RPE is associated with several pathogenic conditions such as Age Related Macular Degeneration and Retinitis Pigmentosa. RPE derived from human embryonic stem cells (hESC) offer a potential source for producing these cells for therapy. Here we report the molecular and cellular characterization of RPE differentiated from hESC. hESC derived RPE are capable of proliferation and lose their epithelial characteristics before becoming confluent and re-differentiating back into their typical pigmented, cobblestoned appearance. During the proliferative phase, they adopt a mesenchymal morphology and express mesenchymal markers. Our results demonstrate that this apparent Epithelial-Mesenchymal Transition is not regulated by the classical EMT transcription factors SNAIL and SLUG. Furthermore, it is possible to regulate RPE de-differentiation and re-differentiation by modulating the Wnt and BMP pathway respectively. These findings further our understanding of the genesis and expansion of RPE which is essential for their therapeutic use.
2012-10-24 | E-MTAB-854 | biostudies-arrayexpress
Project description:Retinal Pigment Epithelial (RPE) cells are located behind the retina and are critical for photoreceptor survival. Loss of RPE is associated with several pathogenic conditions such as Age Related Macular Degeneration and Retinitis Pigmentosa. RPE derived from human embryonic stem cells (hESC) offer a potential source for producing these cells for therapy. Here we report the molecular and cellular characterization of RPE differentiated from hESC. hESC derived RPE are capable of proliferation and lose their epithelial characteristics before becoming confluent and re-differentiating back into their typical pigmented, cobblestoned appearance. During the proliferative phase, they adopt a mesenchymal morphology and express mesenchymal markers. Our results demonstrate that this apparent Epithelial-Mesenchymal Transition is not regulated by the classical EMT transcription factors SNAIL and SLUG. Furthermore, it is possible to regulate RPE de-differentiation and re-differentiation by modulating the Wnt and BMP pathway respectively. These findings further our understanding of the genesis and expansion of RPE which is essential for their therapeutic use.
2013-01-17 | E-MTAB-960 | biostudies-arrayexpress
Project description:Reversal of persistent wound-induced retinal pigmented epithelial-to-mesenchymal transition by the TGFb pathway inhibitor, A-83-01.
| PRJNA281448 | ENA
Project description:Microarray study comparing trabecular meshwork-derived cells (TMDCs) from the iridocorneal angle of the human eye, with other human cell types such as scleral fibroblasts, corneal fibroblasts, retinal pigmented epithelial (RPE) cells, corneal stroma, human embryonic stem cells (hESC), neural precursors differentiated from hESC, human umbilical vein endothelial (HUVEC) cells and human adipose-tissue-derived mesenchymal stromal cells (MSC)
2012-05-01 | GSE28679 | GEO
Project description:Our purpose was to investigate genes and molecular mechanisms involved in patients with Leber congenital amaurosis (LCA). Fibroblasts from two unrelated clinically-identified patients (Coriell) were reprogrammed to pluripotency by retroviral transduction. These human induced Pluripotent Stem Cells (hiPSCs) were differentiated into neural stem cells (NSC) that mimicked the neural tube stage and retinal pigmented epithelial (RPE) cells that could be targeted by the disease. A genome wide transcriptome analysis was performed with Affymetrix Exon Array GeneChipM-BM-., comparing LCA-hiPSCs derivatives to controls. The aim was to identify differentially expressed genes which may be associated with early developmental defect before the establishment of mature retinal circuitry. We analyzed iPSC-derived retinal pigmented epithelial (RPE) cells from LCA patient's fibroblast (n=2) and iPSC-derivedretinal pigmented epithelial (RPE) cells from healthy people fibroblast (n=2). A total of 13 samples were analyzed : 9 RPE cells derived from iPSC LCA and 4 RPE cells derived from wild-type iPSC.
2015-01-21 | E-GEOD-43926 | biostudies-arrayexpress
Project description:Microarray study comparing trabecular meshwork-derived cells (TMDCs) from the iridocorneal angle of the human eye, with other human cell types such as scleral fibroblasts, corneal fibroblasts, retinal pigmented epithelial (RPE) cells, corneal stroma, human embryonic stem cells (hESC), neural precursors differentiated from hESC, human umbilical vein endothelial (HUVEC) cells and human adipose-tissue-derived mesenchymal stromal cells (MSC) 19 samples were analysed, including 6 biological replicates of TMDC, 2 biological replicates of scleral fibroblasts, 3 biological replicates of hAd-MSC
2012-04-30 | E-GEOD-28679 | biostudies-arrayexpress
Project description:Effects of Smad3 and Smad2 knock-down on TGFbeta-induced epithelial-to-mesenchymal transition (EMT) in mouse mammary epithelial (Nme) cells
2009-04-01 | E-MEXP-1342 | biostudies-arrayexpress
Project description:Zika Virus (ZIKV) induces ocular complications in infants born from ZIKV infected mothers during pregnancy. We previously reported that ZIKV is permeable to cells lining the blood-retinal barrier. In this study, we measure the alteration of host transcriptome by ZIKV using primary retinal pigmented epithelial (RPE) cells.
2022-03-18 | GSE169066 | GEO