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  3. Bipotent transitional liver progenitor cells contribute to liver regeneration

Bipotent transitional liver progenitor cells contribute to liver regeneration

  • Nat Genet. 2023 Mar 13. doi: 10.1038/s41588-023-01335-9.
Wenjuan Pu # 1,  Huan Zhu # 1,  Mingjun Zhang # 1,  Monika Pikiolek 2,  Caner Ercan 3,  Jie Li 1,  Xiuzhen Huang 1,  Ximeng Han 1,  Zhenqian Zhang 1,  Zan Lv 1,  Yan Li 1,  Kuo Liu 4,  Lingjuan He 5,  Xiuxiu Liu 1,  Markus H Heim 6 7,  Luigi M Terracciano 8 9,  Jan S Tchorz 10,  Bin Zhou 11 12 13 14
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 2 Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
  • 3 Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • 4 Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
  • 5 School of Life Sciences, Westlake University, Hangzhou, China.
  • 6 Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
  • 7 Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.
  • 8 Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • 9 IRCCS Humanitas Research Hospital, Milan, Italy.
  • 10 Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland. jan.tchorz@novartis.com.
  • 11 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. zhoubin@sibs.ac.cn.
  • 12 Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. zhoubin@sibs.ac.cn.
  • 13 School of Life Science and Technology, ShanghaiTech University, Shanghai, China. zhoubin@sibs.ac.cn.
  • 14 New Cornerstone Science Laboratory, Shenzhen, China. zhoubin@sibs.ac.cn.
  • # Contributed equally.
PMID: 36914834 DOI: 10.1038/s41588-023-01335-9
Abstract

Following severe liver injury, when hepatocyte-mediated regeneration is impaired, biliary epithelial cells (BECs) can transdifferentiate into functional hepatocytes. However, the subset of BECs with such facultative tissue stem cell potential, as well as the mechanisms enabling transdifferentiation, remains elusive. Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe liver injury. By applying a dual genetic lineage tracing approach, we specifically labeled TLPCs and found that they are bipotent, as they either differentiate into hepatocytes or re-adopt BEC fate. Mechanistically, Notch and Wnt/β-catenin signaling orchestrate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively. Together, our study provides functional and mechanistic insights into transdifferentiation-assisted liver regeneration.

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