A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts  

作　　者：Bingqing Xie Da Sun Yuanyuan Du Jun Jia Shicheng Sun Jun Xu Yifang Liu Chengang Xiang Sitong Chen Huangfan Xie Qiming Wang Guangya Li Xuehui LYU Hui Shen Shiyu Li Min Wu Xiaonan Zhang Yue Pu Kuanhui Xiang Weifeng Lai Peng Du Zhenghong Yuan Cheng Li Yan Shi Shichun Lu Hongkui Deng 

机构地区：[1]School of Basic Medical Sciences,State Key Laboratory of Natural and Biomimetic Drugs,Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation,College of Life Sciences,Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100191,China [2]State Key Laboratory of Chemical Oncogenomics,School of Chemical Biology & Biotechnology,Peking University Shenzhen Graduate School,Shenzhen,Guangdong 518055,China [3]Center for Bioinformatics,Peking University,Beijing 100871,China [4]MOE Key Laboratory of Cell Proliferation and Differentiation,College of Life Sciences,Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China [5]Shanghai Public Health Clinical Center,Shanghai 201508,China [6]Hangzhou Repugene Technology Co,. Ltd,Hangzhou,China [7]School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China [8]Key Laboratory of Medical Molecular Virology,Fudan University,Shanghai 200032,China [9]Department of Hepatobiliary Surgery,Chinese PLA General Hospital,Beijing 100853,China

出　　处：《Cell Research》2019年第9期696-710,共15页细胞研究（英文版）

基　　金：We thank Prof. Tungtien Sun for the guidance of the written manuscript. This work was supported by National Key Research and Development Program of China (2017YFA0104003,2017YFA0103000,2018YFA0108102);National Natural Science Foundation of China(31730059,31521004,81670590);SLS-Qidong Innovation Fund(2016000663);National Basic Research Program of China(973 Program 2015CB964703).

摘　　要：Terminally differentiated cells can be generated by lineage reprogramming,which is,however,hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.

关 键 词：hepatic progenitor-like cells (hHPLCs) primary human HEPATOCYTES (PHHs) FIBROBLASTS 

分 类 号：Q[生物学]