Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.
Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.
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DOI：
10.1016/j.stem.2014.09.008
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发表时间：
2014-11-06
期刊：
影响因子：
23.9
通讯作者：
Grompe, Markus
中科院分区：
文献类型：
--
作者：
Tarlow, Branden D.;Pelz, Carl;Naugler, Willscott E.;Wakefield, Leslie;Wilson, Elizabeth M.;Finegold, Milton J.;Grompe, Markus
成体肝脏祖细胞是胆管样上皮细胞，仅在肝脏门静脉周围区域的损伤条件下出现。它们表现出肝细胞和胆管的表型。然而，它们的起源及其对损伤修复的意义仍不清楚。在这里，我们使用嵌合谱系追踪系统来证明肝细胞对祖细胞库有贡献。 RNA测序、超微结构分析和体外祖细胞测定表明，肝细胞来源的祖细胞与胆汁来源的对应物不同。体内谱系追踪和连续移植测定表明，肝细胞衍生的增殖管保留了其起源的记忆，并在损伤停止后分化回肝细胞。同样，嵌合小鼠的人肝细胞也在体内产生胆道祖细胞。我们得出的结论是，人类和小鼠肝细胞可以因损伤而发生可逆的导管化生，扩张为导管，随后有助于肝细胞质量的恢复。
Adult liver progenitor cells are biliary-like epithelial cells that emerge only under injury conditions in the periportal region of the liver. They exhibit phenotypes of both hepatocytes and bile ducts. However, their origin and their significance to injury repair remain unclear. Here, we used a chimeric lineage tracing system to demonstrate that hepatocytes contribute to the progenitor pool. RNA-sequencing, ultrastructural analysis, and in vitro progenitor assays revealed that hepatocyte-derived progenitors were distinct from their biliary-derived counterparts. In vivo lineage tracing and serial transplantation assays showed that hepatocyte-derived proliferative ducts retained a memory of their origin and differentiated back into hepatocytes upon cessation of injury. Similarly, human hepatocytes in chimeric mice also gave rise to biliary progenitors in vivo. We conclude that human and mouse hepatocytes can undergo reversible ductal metaplasia in response to injury, expand as ducts and subsequently contribute to restoration of the hepatocyte mass.
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