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

Ximeng Han; Yue Wang; Wenjuan Pu; Xiuzhen Huang; Lin Qiu; Yan Li; Wei Yu; Huan Zhao; Xiuxiu Liu; Lingjuan He; Libo Zhang; Yong Ji; Jie Lu; Kathy O. Lui; Bin Zhou

Stem Cell Reports (Mar 2019)

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

Ximeng Han,
Yue Wang,
Wenjuan Pu,
Xiuzhen Huang,
Lin Qiu,
Yan Li,
Wei Yu,
Huan Zhao,
Xiuxiu Liu,
Lingjuan He,
Libo Zhang,
Yong Ji,
Jie Lu,
Kathy O. Lui,
Bin Zhou

Affiliations

Ximeng Han: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Yue Wang: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Wenjuan Pu: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Xiuzhen Huang: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Lin Qiu: Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Yan Li: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Wei Yu: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Huan Zhao: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Xiuxiu Liu: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Lingjuan He: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Libo Zhang: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Yong Ji: The Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211100, China; Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211100, China
Jie Lu: Department of Gastroenterology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding author
Kathy O. Lui: Department of Chemical Pathology; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR 999077, China
Bin Zhou: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Nutrition and Metabolism, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; The Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211100, China; Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Corresponding author

Journal volume & issue: Vol. 12, no. 3
pp. 624 – 638

Abstract

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Summary: 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. : In this article, Zhou and colleagues developed an intersectional genetic strategy to specifically label SOX9+ hepatocytes. Using a dual recombinase-mediated Confetti reporter, they showed that a subset of SOX9+ hepatocytes, at single-cell level, are bipotent progenitors that differentiate into both hepatocytes and biliary epithelial cells during liver injury and repair. Keywords: lineage tracing, intersectional genetic strategy, clonal analysis, liver repair and liver regeneration, bipotent progenitors

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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