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首页> 外文期刊>Nature >Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration
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Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration

机译：胆管细胞在肝细胞再生受损期间充当兼性肝干细胞

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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.
机译：肝损伤后，通过肝细胞的自我复制发生再生。在严重的肝损伤中，肝细胞增殖受到损害-人类慢性肝病的特征（1,2）。尚不清楚其他肝细胞类型是否可以再生肝细胞（3-5）。在这里，我们使用两个独立的系统来损害肝损伤期间肝细胞增殖，以评估非肝细胞对实质再生的贡献。首先，由于肝损伤而使肝细胞中的β1-整联蛋白缺失会触发胆管细胞起源的导管反应，其中约25％的肝细胞来自非肝细胞起源。第二，追溯了胆管细胞的谱系，并同时抑制了β1-整合素的敲除或p21过表达对肝细胞增殖的抑制作用，导致胆管细胞衍生的肝细胞显着出现。我们描述了一种组合的肝损伤和肝细胞增殖抑制的模型，肝细胞增殖引起从胆管细胞功能性肝细胞再生的生理显着水平。

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  • 来源
    《Nature》 |2017年第7663期|350-354|共5页
  • 作者

    Raven Alexander; Lu Wei-Yu; Man Tak Yung; Ferreira-Gonzalez Sofia; ODuibhir Eoghan; Dwyer Benjamin J.; Thomson John P.; Meehan Richard R.; Bogorad Roman; Koteliansky Victor; Kotelevtsev Yuri; Ffrench-Constant Charles; Boulter Luke; Forbes Stuart J.;

  • 作者单位

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland;

    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland;

    MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA;

    Skolkovo Inst Sci & Technol, Funct Genom & RNAi Therapy CREI, 3 Nobel St, Skolkovo 143026, Moscow Region, Russia;

    Skolkovo Inst Sci & Technol, Funct Genom & RNAi Therapy CREI, 3 Nobel St, Skolkovo 143026, Moscow Region, Russia;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland;

    Univ Edinburgh, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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