Lineage Tracing Reveals the Bipotency of SOX9+ Hepatocytes during Liver Regeneration
2019
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
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
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