学科主题基础医学
Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming
Du, Yuanyuan1; Wang, Jinlin2; Jia, Jun1,2; Song, Nan1,2; Xiang, Chengang1; Xu, Jun1; Hou, Zhiyuan4; Su, Xiaohua1; Liu, Bei2; Jiang, Tao5; Zhao, Dongxin1; Sun, Yingli6; Shu, Jian1; Guo, Qingliang5; Yin, Ming1; Sun, Da2; Lu, Shichun5; Shi, Yan2; Deng, Hongkui1,2,3
刊名CELL STEM CELL
2014-03-06
DOI10.1016/j.stem.2014.01.008
14期:3页:394-403
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell & Tissue Engineering ; Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]CELL-DERIVED HEPATOCYTES ; PANCREAS PROGENITORS ; LIVER ; DIFFERENTIATION ; MATURATION ; SYSTEMS
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.

语种英语
WOS记录号WOS:000332533400015
项目编号973 Program 2012CB966401 ; 2011AA020107 ; 2013DFG30680 ; Z121100005212001 ; 2011ZX09102-010-03 ; 1023963 ; 37871
资助机构National Basic Research Program of China ; Ministry of Science and Technology ; Science and Technology Commission of Beijing ; Key New Drug Creation and Manufacturing Program ; Ministry of Education of China (111 Project) ; Bill &amp ; Melinda Gates Foundation
引用统计
被引频次:120[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51504
专题北京大学临床肿瘤学院_移植与免疫治疗病区
北京大学基础医学院
北京大学临床肿瘤学院_妇科肿瘤科
作者单位1.Beijing Vitalstar Biotechnol, Beijing 100012, Peoples R China
2.Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Life Sci, MOE Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
3.Peking Univ, Shenzhen Grad Sch, Key Lab Chem Genom, Shenzhen Stem Cell Engn Lab, Shenzhen 518055, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Peking Univ Stem Cell Res Ctr,Dept Cell Biol, Beijing 100191, Peoples R China
5.Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, Beijing 100853, Peoples R China
6.Chinese Acad Sci, Beijing Inst Genom, Lab Genome Variat & Precis Biomed, Beijing 100101, Peoples R China
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,2014,14(3):394-403.
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,14(3),394-403.
MLA Du, Yuanyuan,et al."Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming".CELL STEM CELL 14.3(2014):394-403.
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