Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell–Derived RPE
dc.contributor.author | Sripathi, Srinivasa R. | |
dc.contributor.author | Hu, Ming-Wen | |
dc.contributor.author | Liu, Melissa M. | |
dc.contributor.author | Wan, Jun | |
dc.contributor.author | Cheng, Jie | |
dc.contributor.author | Duan, Yukan | |
dc.contributor.author | Mertz, Joseph L. | |
dc.contributor.author | Wahlin, Karl J. | |
dc.contributor.author | Maruotti, Julien | |
dc.contributor.author | Berlinicke, Cynthia A. | |
dc.contributor.author | Qian, Jiang | |
dc.contributor.author | Zack, Donald J. | |
dc.contributor.department | Medical and Molecular Genetics, School of Medicine | en_US |
dc.date.accessioned | 2022-08-26T11:16:58Z | |
dc.date.available | 2022-08-26T11:16:58Z | |
dc.date.issued | 2021-04 | |
dc.description.abstract | Purpose: RPE injury often induces epithelial to mesenchymal transition (EMT). Although RPE-EMT has been implicated in a variety of retinal diseases, including proliferative vitroretinopathy, neovascular and atrophic AMD, and diabetic retinopathy, it is not well-understood at the molecular level. To contribute to our understanding of EMT in human RPE, we performed a time-course transcriptomic analysis of human stem cell-derived RPE (hRPE) monolayers induced to undergo EMT using 2 independent, yet complementary, model systems. Methods: EMT of human stem cell-derived RPE monolayers was induced by either enzymatic dissociation or modulation of TGF-β signaling. Transcriptomic analysis of cells at different stages of EMT was performed by RNA-sequencing, and select findings were confirmed by reverse transcription quantitative PCR and immunostaining. An ingenuity pathway analysis (IPA) was performed to identify signaling pathways and regulatory networks associated with EMT. Results: Proteocollagenolytic enzymatic dissociation and cotreatment with TGF-β and TNF-α both induce EMT in human stem cell-derived RPE monolayers, leading to an increased expression of mesenchymal factors and a decreased expression of RPE differentiation-associated factors. Ingenuity pathway analysis identified the upstream regulators of the RPE-EMT regulatory networks and identified master switches and nodes during RPE-EMT. Of particular interest was the identification of widespread dysregulation of axon guidance molecules during RPE-EMT progression. Conclusions: The temporal transcriptome profiles described here provide a comprehensive resource of the dynamic signaling events and the associated biological pathways that underlie RPE-EMT onset. The pathways defined by these studies may help to identify targets for the development of novel therapeutic targets for the treatment of retinal disease. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Sripathi SR, Hu MW, Liu MM, et al. Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell-Derived RPE. Invest Ophthalmol Vis Sci. 2021;62(4):1. doi:10.1167/iovs.62.4.1 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/29898 | |
dc.language.iso | en_US | en_US |
dc.publisher | Association for Research in Vision and Ophthalmology | en_US |
dc.relation.isversionof | 10.1167/iovs.62.4.1 | en_US |
dc.relation.journal | Investigative Ophthalmology & Visual Science | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | Stem cells | en_US |
dc.subject | Differentiation | en_US |
dc.subject | Retinal pigment epithelium | en_US |
dc.subject | Epithelial–mesenchymal transition | en_US |
dc.subject | TGF-β/TNF-α | en_US |
dc.subject | Transcriptomics | en_US |
dc.title | Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell–Derived RPE | en_US |
dc.type | Article | en_US |