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 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.
Stem Cell Reports. 2019 Mar 5;12(3):624-638. doi: 10.1016/j.stemcr.2019.01.010. Epub 2019 Feb 14.
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.
阐明不同细胞谱系在肝脏中的作用可能为肝脏再生提供途径。先前的研究表明,SOX9 肝细胞在肝损伤后可以分化为胆管细胞。目前尚不清楚 SOX9 肝细胞在肝损伤时是否是具有单一或双重潜能的祖细胞。在这里,我们开发了一种遗传追踪系统来描绘 SOX9 肝细胞在肝内稳态和再生过程中的谱系潜能。命运图谱数据显示,这些 SOX9 肝细胞对不同的肝损伤有特异性反应,其中一些细胞大量参与到胆管细胞的生成中。克隆分析表明,单个 SOX9 肝细胞在肝损伤后可以产生肝细胞和胆管细胞。这项研究提供了直接证据,表明 SOX9 肝细胞在肝损伤后可以作为双重潜能祖细胞,为肝脏修复和再生产生肝细胞和胆管细胞。