Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration

Article

关键词: HEPATIC PROGENITOR CELLS;    INJURY;    MICE;    BETA-1-INTEGRIN;    ACTIVATION;    FIBROSIS;    ABLATION;    DISEASES;    ORIGIN;   

DOI  :  10.1038/nature23015

来源: SCIE

【 摘 要 】

After liver injury, regeneration occurs through self-replication of hepatocytes. In severe liver injury, hepatocyte proliferation is impaired-a feature of human chronic liver disease(1,2). It is unclear whether other liver cell types can regenerate hepatocytes(3-5). Here we use two independent systems to impair hepatocyte proliferation during liver injury to evaluate the contribution of non-hepatocytes to parenchymal regeneration. First, loss of beta 1-integrin in hepatocytes with liver injury triggered a ductular reaction of cholangiocyte origin, with approximately 25% of hepatocytes being derived from a non-hepatocyte origin. Second, cholangiocytes were lineage traced with concurrent inhibition of hepatocyte proliferation by beta 1-integrin knockdown or p21 overexpression, resulting in the significant emergence of cholangiocyte-derived hepatocytes. We describe a model of combined liver injury and inhibition of hepatocyte proliferation that causes physiologically significant levels of regeneration of functional hepatocytes from biliary cells.

【 授权许可】

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