Cell Proliferation >

2024 , Vol. 57 >Issue 2: 0

DOI: https://doi.org/10.1111/cpr.13540

The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells

  • Yun Lv 1 ,
  • Ziyan Rao 2,3 ,
  • Lulu Liu 4 ,
  • Jun Jia 5 ,
  • Chenyang Wu 2,3 ,
  • Jun Xu 6 ,
  • Yuanyuan Du 1 ,
  • Yinan Liu 6 ,
  • Bei Liu 1 ,
  • Jihang Shi 7 ,
  • Guangya Li 8 ,
  • Dongyu Zhao , 2,3 ,
  • Hongkui Deng , 1,5
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  • 1. School of Basic Medical Sciences, MOE Engineering Research Center of Regenerative Medicine, 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, China
  • 2. Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
  • 3. State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
  • 4. Peking University-Tsinghua University-National Institute of Biological Science Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
  • 5. Changping Laboratory, Beijing, China
  • 6. Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University Health Science Center, Peking University, Beijing, China
  • 7. Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
  • 8. Ministry of Education (MOE) Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
zhaodongyu@bjmu.edu.cn
hongkui_deng@pku.edu.cn

Received date: 23 May 2023

Revised date: 08 Aug 2023

Accepted date: 21 Aug 2023

Copyright

2023 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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Abstract

Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.

Cite this article

Yun Lv , Ziyan Rao , Lulu Liu , Jun Jia , Chenyang Wu , Jun Xu , Yuanyuan Du , Yinan Liu , Bei Liu , Jihang Shi , Guangya Li , Dongyu Zhao , Hongkui Deng . The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells[J]. Cell Proliferation, 2024 , 57(2) : e13540 . DOI: 10.1111/cpr.13540

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