{"doi":"10.1167/iovs.62.4.1","title":"Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell–Derived RPE","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.","journal":"Investigative Ophthalmology & Visual Science","year":2021,"id":169190,"datarank":0.519860385419959,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.0,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9288,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322055,"name":"Ming-Wen Hu","orcid":null,"position":1,"is_corresponding":false},{"id":699536,"name":"Melissa M. Liu","orcid":"0000-0002-4385-9507","position":2,"is_corresponding":false},{"id":300846,"name":"Jun Wan","orcid":"0000-0001-9286-6562","position":3,"is_corresponding":false},{"id":397795,"name":"Jie Cheng","orcid":"0000-0002-8835-3171","position":4,"is_corresponding":false},{"id":699537,"name":"Yukan Duan","orcid":"0000-0001-9614-8402","position":5,"is_corresponding":false},{"id":532236,"name":"Joseph Mertz","orcid":"0000-0003-3158-809X","position":6,"is_corresponding":false},{"id":335089,"name":"Karl Wahlin","orcid":"0000-0002-0494-8304","position":7,"is_corresponding":false},{"id":699538,"name":"Julien Maruotti","orcid":"0000-0003-2290-7538","position":8,"is_corresponding":false},{"id":280703,"name":"Cynthia Berlinicke","orcid":"0000-0003-1014-0800","position":9,"is_corresponding":false},{"id":268678,"name":"Jiang Qian","orcid":"0000-0002-0476-3596","position":10,"is_corresponding":false},{"id":6902,"name":"Donald J. Zack","orcid":"0000-0002-7966-1973","position":11,"is_corresponding":false},{"id":699535,"name":"Srinivas R. Sripathi","orcid":"0000-0001-6834-553X","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:11.334362Z","pmid":"33792620","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}