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Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming
Du, Yuanyuan ; Wang, Jinlin ; Jia, Jun ; Song, Nan ; Xiang, Chengang ; Xu, Jun ; Hou, Zhiyuan ; Su, Xiaohua ; Liu, Bei ; Jiang, Tao ; Zhao, Dongxin ; Sun, Yingli ; Shu, Jian ; Guo, Qingliang ; Yin, Ming ; Sun, Da ; Lu, Shichun ; Shi, Yan ; Deng, Hongkui
刊名cell stem cell
2014
关键词CELL-DERIVED HEPATOCYTES PANCREAS PROGENITORS LIVER DIFFERENTIATION MATURATION SYSTEMS
DOI10.1016/j.stem.2014.01.008
英文摘要Obtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2(-/-)/gamma c(-/-) mice and secrete more than 300 mu g/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000332533400015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Cell & Tissue Engineering; Cell Biology; SCI(E); PubMed; 86; ARTICLE; lsc620213@aliyun.com; shiyan@pkusz.edu.cn; hongkui_deng@pku.edu.cn; 3; 394-403; 14
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/189424]  
专题生命科学学院
推荐引用方式
GB/T 7714
Du, Yuanyuan,Wang, Jinlin,Jia, Jun,et al. Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming[J]. cell stem cell,2014.
APA Du, Yuanyuan.,Wang, Jinlin.,Jia, Jun.,Song, Nan.,Xiang, Chengang.,...&Deng, Hongkui.(2014).Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming.cell stem cell.
MLA Du, Yuanyuan,et al."Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming".cell stem cell (2014).
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