Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion

Xingrui Wang; Wenjuan Pu; Huan Zhu; Mingjun Zhang; Bin Zhou

doi:10.52601/bpr.2023.230034

Volume 9 Issue 6

Dec. 2023

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Article Navigation > Biophysics Reports > 2023 > 9(6): 309-324

Xingrui Wang, Wenjuan Pu, Huan Zhu, Mingjun Zhang, Bin Zhou. Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion[J]. Biophysics Reports, 2023, 9(6): 309-324. doi: 10.52601/bpr.2023.230034

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Xingrui Wang, Wenjuan Pu, Huan Zhu, Mingjun Zhang, Bin Zhou. Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion[J]. Biophysics Reports, 2023, 9(6): 309-324. doi: 10.52601/bpr.2023.230034

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Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion

doi: 10.52601/bpr.2023.230034

Xingrui Wang¹,
Wenjuan Pu¹,
Huan Zhu¹,
Mingjun Zhang¹,
Bin Zhou^{1, 2, 3
,
,}

1.
New Cornerstone Science Laboratory, 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 200031, China
2.
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 310024, China
3.
School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China

More Information

Corresponding author: zhoubin@sibs.ac.cn (B. Zhou)
Received Date: 07 November 2023
Accepted Date: 22 January 2024

Available Online: 05 March 2024

Publish Date: 31 December 2023

Abstract

Abstract

The liver consists predominantly of hepatocytes and biliary epithelial cells (BECs), which serve distinct physiological functions. Although hepatocytes primarily replenish their own population during homeostasis and injury repair, recent findings have suggested that BECs can transdifferentiate into hepatocytes when hepatocyte-mediated liver regeneration is impaired. However, the cellular and molecular mechanisms governing this BEC-to-hepatocyte conversion remain poorly understood largely because of the inefficiency of existing methods for inducing lineage conversion. Therefore, this study introduces a novel mouse model engineered by the Zhou's lab, where hepatocyte senescence is induced by the deletion of the fumarylacetoacetate (Fah) gene. This model facilitates the efficient conversion of BECs to hepatocytes and allows for the simultaneous lineage tracing of BECs; consequently, a transitional liver progenitor cell population can be identified during lineage conversion. This study also outlines the technical procedures for utilizing this model to determine the underlying cellular and molecular mechanisms of BEC-to-hepatocyte conversion and provides new insights into liver regeneration and its underlying molecular mechanism.
- Liver regeneration,
- BEC-to-hepatocyte transdifferentiation,
- Fumarylacetoacetate (Fah) gene,
- Transitional liver progenitor cells (TLPC),
- Lineage tracing

The authors declare that they have no conflicts of interest.
All institutional and national guidelines for the care and use of laboratory animals were followed.

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