Genetic tracing of hepatocytes in liver homeostasis, injury, and regeneration

Genetic tracing of hepatocytes in liver homeostasis, injury, and regeneration
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肝细胞在肝脏稳态、损伤和再生中的基因追踪

DOI:
10.1074/jbc.m117.782029
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发表时间:
2017-04
期刊:
Journal Biological Chemistry
影响因子:
--
通讯作者:
Bin Zhou
Bin Zhou
中科院分区:
其他
文献类型:
--
作者:
Yue Wang;Xiuzhen Huang;Lingjuan He;Wenjuan Pu;Yan Li;Qiaozhen Liu;Yi Li;Libo Zhang;Wei Yu;Huan Zhao;Yingqun Zhou;Bin Zhou

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The liver possesses a remarkable capacity to regenerate after damage. There is a heated debate on the origin of new hepatocytes after injuries in adult liver. Hepatic stem/progenitor cells have been proposed to produce functional hepatocytes after injury. Recent studies have argued against this model and suggested that pre-existing hepatocytes, rather than stem cells, contribute new hepatocytes. This hepatocyte-to-hepatocyte model is mainly based on labeling of hepatocytes with Cre-recombinase delivered by the adeno-associated virus. However, the impact of virus infection on cell fate determination, consistency of infection efficiency, and duration of Cre-virus in hepatocytes remain confounding factors that interfere with the data interpretation. Here, we generated a new genetic tool Alb-DreER to label almost all hepatocytes (>99.5%) and track their contribution to different cell lineages in the liver. By “pulse-and-chase” strategy, we found that pre-existing hepatocytes labeled by Alb-DreER contribute to almost all hepatocytes during normal homeostasis and after liver injury. Virtually all hepatocytes in the injured liver are descendants of pre-existing hepatocytes through self-expansion. We concluded that stem cell differentiation is unlikely to be responsible for the generation of a substantial number of new hepatocytes in adult liver. Our study also provides a new mouse tool for more precise in vivo genetic study of hepatocytes in the field.
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影响因子: 13.5
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