Wang Xingrui, Pu Wenjuan, Zhu Huan, Zhang Mingjun, Zhou Bin
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.
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.
Biophys Rep. 2023 Dec 31;9(6):309-324. doi: 10.52601/bpr.2023.230034.
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 () 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.
肝脏主要由肝细胞和胆管上皮细胞（BECs）组成，它们具有不同的生理功能。虽然肝细胞在稳态和损伤修复过程中主要补充自身细胞群，但最近的研究结果表明，当肝细胞介导的肝脏再生受损时，BECs可以转分化为肝细胞。然而，由于现有诱导谱系转化方法效率低下，控制这种BEC向肝细胞转化的细胞和分子机制仍知之甚少。因此，本研究介绍了周实验室构建的一种新型小鼠模型，其中通过缺失富马酰乙酰乙酸（）基因诱导肝细胞衰老。该模型有助于BECs高效转化为肝细胞，并允许对BECs进行同时谱系追踪；因此，在谱系转化过程中可以识别出一个过渡性肝祖细胞群体。本研究还概述了利用该模型确定BEC向肝细胞转化潜在细胞和分子机制的技术程序，并为肝脏再生及其潜在分子机制提供了新的见解。
