{"doi":"10.1016/j.cmet.2021.05.015","title":"SARS-CoV-2 infection induces beta cell transdifferentiation","abstract":"Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.","journal":"Cell Metabolism","year":2021,"id":146781,"datarank":0.7932400546041803,"base_score":5.288267030694535,"endowment":5.288267030694535,"self_citation_contribution":0.7932400546041803,"citation_network_contribution":0.0,"self_endowment_contribution":0.7932400546041803,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":197,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"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":103710,"name":"Skyler Uhl","orcid":"0000-0001-8517-1455","position":1,"is_corresponding":false},{"id":109215,"name":"Tuo Zhang","orcid":"0000-0001-5396-918X","position":2,"is_corresponding":false},{"id":623865,"name":"Dongxiang Xue","orcid":"0000-0001-9654-6347","position":3,"is_corresponding":false},{"id":611008,"name":"Bo Li","orcid":"0000-0002-4456-7303","position":4,"is_corresponding":false},{"id":399382,"name":"J. 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