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Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. <jats:italic>In vitro<\/jats:italic> cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Transcriptional analyses showed that PZ induces oxidative stress (OS) in HLCs in general, but in HLCs from susceptible individuals, PZ causes relative disruption of iron metabolism and higher burden of OS. Our study establishes the first patient-specific HLC-based platform for idiosyncratic hepatotoxicity testing, incorporating multiple potential causative factors and permitting the correlation of transcriptomic and cellular responses to clinical phenotypes. Establishment of patient-specific HLCs with clinical phenotypes representing population variations will be valuable for pharmaceutical drug testing.<\/jats:p>","DOI":"10.1038\/srep41238","type":"journal-article","created":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T10:22:56Z","timestamp":1485339776000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity"],"prefix":"10.1038","volume":"7","author":[{"given":"Yukti","family":"Choudhury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Chin","family":"Toh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwa","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghua","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Poh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Shan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindran","family":"Kanesvaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanry","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Han","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,25]]},"reference":[{"key":"BFsrep41238_CR1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1586\/17474124.2014.922871","volume":"8","author":"M Chen","year":"2015","unstructured":"Chen, M., Borlak, J. & Tong, W. 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The error has not been fixed in the paper. In addition, the version of this Article previously published omitted Hanry Yu as a corresponding author. Correspondence and request for materials should also be addressed to hyu@ibn.a-star.edu.sg. This has now been corrected in the HTML and PDF versions of the Article.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2017","order":7,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Erratum","order":8,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Scientific Reports 7: Article number: 41238; published online: 25 January 2017; updated: 25 April 2017 The original version of this Article contained an error in the spelling of the author Huan Li, which was incorrectly given as Li Huan. The Author Contributions Statement, Study concept and design: Y.","order":9,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ravindran Kanesvaran has received research funding from Sanofi and is on advisory board of Pfizer, Astellas and Bayer. Hanry Yu has ownership in and is on advisory board of InvitroCue Pte Ltd and has received research funding from Janssen. Min-Han Tan has received research funding from Pfizer. Yukti Choudhury and Min-Han Tan have filed a patent filed for a patent involving molecular diagnostics in renal cell carcinoma. The remaining authors have declared no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41238"}}