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Cited by 113Liver physiology and pathologyMesenchymal stem cell researchCongenital heart defects research

Lineage Tracing Reveals the Bipotency of SOX9+ Hepatocytes during Liver Regeneration

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Han, Ximeng, Wang, Yue, Pu, Wenjuan, Huang, Xiuzhen, Qiu, Lin, Li, Yan, Yu, Wei, Zhao, Huan +7 more·2019·Stem Cell Reports
DOI 10.1016/j.stemcr.2019.01.010PMC PMC6409431
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Abstract

Elucidation of the role of different cell lineages in the liver could offer avenues to drive liver regeneration. Previous studies showed that SOX9 + hepatocytes can differentiate into ductal cells after liver injuries. It is unclear whether SOX9 + hepatocytes are uni- or bipotent progenitors at a single-cell level during liver injury. Here, we developed a genetic tracing system to delineate the lineage potential of SOX9 + hepatocytes during liver homeostasis and regeneration. Fate-mapping data showed that these SOX9 + hepatocytes respond specifically to different liver injuries, with some contributing to a substantial number of ductal cells. Clonal analysis demonstrated that a single SOX9 + hepatocyte gives rise to both hepatocytes and ductal cells after liver injury. This study provides direct evidence that SOX9 + hepatocytes can serve as bipotent progenitors after liver injury, producing both hepatocytes and ductal cells for liver repair and regeneration.

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  • YAP activation in liver regeneration reprograms a subset of periportal hepatocytes into SOX9+ progenitor-like cells that can give rise to both cholangiocytes and hepatocytes.

    “YAP activation in liver regeneration has been shown to reprogram a subset of periportal hepatocytes into SOX9+ progenitor-like cells (PLCs) that can give rise to both cholangiocytes and hepatocytes (51, 52).”

    From Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 (2022) · cites this paper as [51]

    The Results identify SOX9+ cells among periportal hepatocytes, and the Discussion reports that a single SOX9+ hepatocyte can give rise to both biliary epithelial cells (cholangiocytes) and hepatocytes after injury. But the Discussion says whether Hippo-YAP signaling is activated in these cells to regulate their bipotency remains to be investigated; this paper does not establish that YAP activation reprograms them. (LLM, conf=0.90)

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Research works printed but not linked: 34

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Authors
Han, X., Wang, Y., Pu, W., Huang, X., Qiu, L., Li, Y., Yu, W., Zhao, H., Liu, X., He, L., Zhang, L., Ji, Y., Lu, J., Lui, K. O., & Zhou, B.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Nanjing Medical University (CN)
  • Tongji University (CN)
  • Chinese University of Hong Kong (HK)
  • Jinan University (CN)
Corresponding author
  • Lu, Jie
  • Zhou, Bin
ORCID
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2019-03
Volume
12
Issue
3
Pages
624-638
ISSN
2213-6711 (ISSN-L)
DOI
10.1016/j.stemcr.2019.01.010
PMC
PMC6409431
OpenAlex
W2913695690
Cited by
113
References
42
Citations by year
2026: 4 · 2025: 16 · 2024: 16 · 2023: 14 · 2022: 19 · 2021: 23 · 2020: 16 · 2019: 5
FWCI
10.04
Type
journal article
Language
en
Update notices
erratum (2025-07-08)
Open access
Licence
Locations
  • Stem Cell Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (91849202, 91639302, 31730112, 31701292, 81872241, 81761138040, 31625019)
  • Youth Innovation Promotion Association of the Chinese Academy of Sciences (QYZDB-SSW-SMC003, 2060299)
  • National Key Research and Development Program of China (2017YFC1001303, 2018YFA0108100, 2018YFA0107900, 2016YFC1300600)
  • China Postdoctoral Science Foundation
  • Boehringer Ingelheim
  • Health and Medical Research Fund (03140346, 04152566)
  • Science and Technology Commission of Shanghai Municipality (17ZR1449600)
  • Chinese Academy of Sciences (XDB19000000, XDA16020204)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
SOX9, hepatocytes, liver regeneration, bipotent progenitors, ductal cells, lineage tracing, fate mapping, clonal analysis, liver injury, liver homeostasis, hepatocyte differentiation
MeSH terms
Animals, Cell Differentiation, Homeostasis, Liver, Liver Diseases, Liver Regeneration, Cell Lineage, Hepatocytes, Mice, SOX9 Transcription Factor

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