IL6 supports long-term expansion of hepatocytes in vitro.
IL6 supports long-term expansion of hepatocytes in vitro.
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IL6 支持肝细胞体外长期扩增
DOI：
10.1038/s41467-022-35167-8
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发表时间：
2022-11-29
影响因子：
16.6
通讯作者：
Xie, Xin
中科院分区：
文献类型：
--
作者：
Guo, Ren;Jiang, Mengmeng;Wang, Gang;Li, Bing;Jia, Xiaohui;Ai, Yan;Chen, Shanshan;Tang, Peilan;Liu, Aijie;Yuan, Qianting;Xie, Xin
肝细胞很难在体外扩增。一些研究已经证明，具有生长因子或Wnt配体的化学鸡尾酒可以通过去分化支持肝细胞的长期扩增。然而，培养条件复杂，具有完全分化能力的肝祖细胞的克隆扩增很少报道。在此，我们发现IL 6与EGF和HGF组合，通过将肝细胞转化为诱导的肝祖细胞（iHPC），促进体外小鼠原代肝细胞在简单的2D培养中的长期扩增（在约150天内>30代，理论扩增约1035倍），所述诱导的肝祖细胞（iHPC）维持向肝细胞分化的能力。IL6还支持单肝细胞衍生的iHPC克隆的建立。下游STAT3、ERK和AKT途径的总和诱导了许多支持快速生长的转录因子。这种生理和简单的方法可能为培养以前难以培养的细胞类型提供思路，并支持其未来的应用。
Hepatocytes are very difficult to expand in vitro. A few studies have demonstrated that chemical cocktails with growth factors or Wnt ligands can support long-term expansion of hepatocytes via dedifferentiation. However, the culture conditions are complex, and clonal expansion of hepatic progenitors with full differentiation capacity are rarely reported. Here, we discover IL6, combined with EGF and HGF, promotes long-term expansion (>30 passages in ~150 days with theoretical expansion of ~1035times) of primary mouse hepatocytes in vitro in simple 2D culture, by converting hepatocytes into induced hepatic progenitor cells (iHPCs), which maintain the capacity of differentiation into hepatocytes. IL6 also supports the establishment of single hepatocyte-derived iHPC clones. The summation of the downstream STAT3, ERK and AKT pathways induces a number of transcription factors which support rapid growth. This physiological and simple way may provide ideas for culturing previously difficult-to-culture cell types and support their future applications.
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人肝细胞来源的肝祖样细胞的扩增和分化及其在嗜肝病原体研究中的应用
影响因子：
44.1
作者：
Fu GB;Huang WJ;Zeng M;Zhou X;Wu HP;Liu CC;Wu H;Weng J;Zhang HD;Cai YC;Ashton C;Ding M;Tang D;Zhang BH;Gao Y;Yu WF;Zhai B;He ZY;Wang HY;Yan HX
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Yan HX
影响因子：
4
作者：
Kreutz C;MacNelly S;Follo M;Wäldin A;Binninger-Lacour P;Timmer J;Bartolomé-Rodríguez MM
通讯作者：
Bartolomé-Rodríguez MM
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影响因子：
5.9
作者：
Guo R;Tang W;Yuan Q;Hui L;Wang X;Xie X
通讯作者：
Xie X
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
--
作者：
AKERMAN, P;COTE, P;DIEHL, AM
通讯作者：
DIEHL, AM