| Title | A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts |
| Authors | Xie, Bingqing Sun, Da Du, Yuanyuan Jia, Jun Sun, Shicheng Xu, Jun Liu, Yifang Xiang, Chengang Chen, Sitong Xie, Huangfan Wang, Qiming Li, Guangya Lyu, Xuehui Shen, Hui Li, Shiyu Wu, Min Zhang, Xiaonan Pu, Yue Xiang, Kuanhui Lai, Weifeng Du, Peng Yuan, Zhenghong Li, Cheng Shi, Yan Lu, Shichun Deng, Hongkui |
| Affiliation | Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Sch Basic Med Sci, Beijing 100191, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Life Sci, MOE Key Lab Cell Proliferat & Differentiat, Beijing 100191, Peoples R China Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, State Key Lab Chem Oncogen, Shenzhen 518055, Guangdong, Peoples R China Peking Univ, Ctr Bioinformat, Beijing 100871, Peoples R China Peking Univ, Coll Life Sci, Peking Tsinghua Ctr Life Sci, MOE Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China Hangzhou Repugene Technol Co Ltd, Hangzhou, Zhejiang, Peoples R China Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China Fudan Univ, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, Beijing 100853, Peoples R China |
| Issue Date | 2019 |
| Publisher | CELL RESEARCH |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/545481 |
| ISSN | 1001-0602 |
| DOI | 10.1038/s41422-019-0196-x |
| Indexed | SCI(E) EI |
| Appears in Collections: | 天然药物与仿生药物国家重点实验室 生命科学学院 细胞增殖分化调控机理研究教育部重点实验室 深圳研究生院待认领 基础医学院 |
