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A large proportion of patients with COVID\u201019 developed liver injuries. The human\u2010induced pluripotent stem cell (iPSC)\u2010derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To explore the susceptibility of hepatocytes to SARS\u2010CoV\u20102, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS\u2010CoV\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The iPSC\u2010derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS\u2010CoV\u20102 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The iPSC\u2010derived hepatocytes can support the replication of SARS\u2010CoV\u20102, and this platform could be used to investigate the SARS\u2010CoV\u20102 hepatotropism and hepatic pathogenic mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgh3.13039","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T07:39:58Z","timestamp":1720769998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human\u2010induced pluripotent stem cell\u2010derived hepatocyte platform in modeling of <scp>SARS\u2010CoV<\/scp>\u20102 infection"],"prefix":"10.1002","volume":"8","author":[{"given":"Ruiqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"},{"name":"Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou China"},{"name":"Center for Translational Stem Cell Biology  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"},{"name":"Center for Translational Stem Cell Biology  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwok\u2010Hung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan Fan\u2010Ngai","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4665-7887","authenticated-orcid":false,"given":"Hung\u2010Fat","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"},{"name":"Center for Translational Stem Cell Biology  Hong Kong SAR China"},{"name":"Cardiac and Vascular Center Hong Kong University Shenzhen Hospital  Shenzhen China"},{"name":"Hong Kong\u2010Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.04.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31404"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2010419"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.6775"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321726"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.26444\/aaem\/142232"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000022818"},{"key":"e_1_2_6_9_1","first-page":"502","article-title":"Fulminant hepatic failure: a rare and devastating manifestation of Coronavirus disease 2019 in an 11\u2010year\u2010old boy","volume":"2020","author":"Haji Esmaeil Memar E","year":"2019","journal-title":"Arch. 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