Lineage Tracing Reveals the Bipotency of SOX9+ Hepatocytes during Liver Regeneration
Lineage Tracing Reveals the Bipotency of SOX9+ Hepatocytes during Liver Regeneration
复制标题
谱系追踪揭示了 SOX9 肝细胞在肝脏再生过程中的双能性
DOI：
10.1016/j.stemcr.2019.01.010
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发表时间：
2019-03-05
影响因子：
5.9
通讯作者：
Zhou, Bin
中科院分区：
文献类型：
--
作者：
Han, Ximeng;Wang, Yue;Zhou, Bin
阐明不同细胞系在肝脏中的作用可以提供驱动肝脏再生的途径。先前的研究表明，SOX9（+）肝细胞在肝损伤后可以分化为导管细胞。目前还不清楚在肝损伤过程中，SOX 9（+）肝细胞在单细胞水平上是单能还是双能祖细胞。在这里，我们开发了一个遗传追踪系统，以描绘在肝脏稳态和再生过程中SOX 9（+）肝细胞的谱系潜力。命运图谱数据显示，这些SOX 9（+）肝细胞对不同的肝损伤有特异性反应，其中一些有助于大量的导管细胞。克隆分析表明，一个单一的SOX 9（+）肝细胞产生肝细胞和导管细胞肝损伤后。这项研究提供了直接的证据，SOX9（+）肝细胞可以作为肝损伤后的双能祖细胞，产生肝细胞和导管细胞用于肝修复和再生。
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.