Contributions of biliary epithelial cells to hepatocyte homeostasis and regeneration in zebrafish.

Contributions of biliary epithelial cells to hepatocyte homeostasis and regeneration in zebrafish.
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胆管上皮细胞对斑马鱼肝细胞稳态和再生的贡献

DOI:
10.1016/j.isci.2021.102142
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发表时间:
2021-03-19
期刊:
影响因子:
5.8
通讯作者:
He J
He J
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Zhang W;Chen J;Ni R;Yang Q;Luo L;He J

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胆管上皮细胞(BEC)向肝细胞的转分化是否在生理条件下发生并有助于肝脏稳态仍存在长期争论。如果纤维化肝脏遭受严重损伤,在病理情况下也会提出类似的问题。为了解决斑马鱼中的这些问题,我们建立了一个灵敏的谱系追踪系统,专门用于检测 BEC 衍生的肝细胞。 BEC 向肝细胞的转分化发生,并成为部分成年个体肝细胞稳态的次要贡献者。 BEC 来源的肝细胞在肝脏中成簇分布。当纤维化肝脏遭受极度肝细胞损伤时,BEC向肝细胞转分化是肝细胞再生的主要来源。相反,部分肝切除术未能诱导 BEC 向肝细胞的转化。总之,基于灵敏的谱系追踪系统,我们的结果表明 BEC 能够转分化为肝细胞,并有助于生理性肝细胞稳态和病理性再生。开发了敏感性系统,可在肝脏稳态中追踪 BEC 衍生的肝细胞 BEC 在肝脏稳态中转化为肝细胞,但个体异质 BEC 是纤维化肝脏极度损伤的主要再生来源 BEC 在部分肝切除后无法生成新的肝细胞 细胞生理学;细胞生物学;发育生物学
Whether transdifferentiation of the biliary epithelial cells (BECs) to hepatocytes occurs under physiological conditions and contributes to liver homeostasis remains under long-term debate. Similar questions have been raised under pathological circumstances if a fibrotic liver is suffered from severe injuries. To address these questions in zebrafish, we established a sensitive lineage tracing system specific for the detection of BEC-derived hepatocytes. The BEC-to-hepatocyte transdifferentiation occurred and became minor contributors to hepatocyte homeostasis in a portion of adult individuals. The BEC-derived hepatocytes distributed in clusters in the liver. When a fibrotic liver underwent extreme hepatocyte damages, BEC-to-hepatocyte transdifferentiation acted as the major origin of regenerating hepatocytes. In contrast, partial hepatectomy failed to induce the BEC-to-hepatocyte conversion. In conclusion, based on a sensitive lineage tracing system, our results suggest that BECs are able to transdifferentiate into hepatocytes and contribute to both physiological hepatocyte homeostasis and pathological regeneration. Developed sensitivity system to trace BECs derived hepatocytes in liver homeostasis BECs convert to hepatocytes in liver homeostasis but are individually heterogeneous BECs are the primary regeneration sources in the extreme injury of the fibrotic liver BECs fail to contribute to new hepatocytes after partial hepatectomy Cellular physiology; cellular biology; developmental biology
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