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IL6 supports long-term expansion of hepatocytes in vitro

Author

Listed:
  • Ren Guo

    (Chinese Academy of Sciences)

  • Mengmeng Jiang

    (Chinese Academy of Sciences
    ShanghaiTech University
    University of Chinese Academy of Sciences)

  • Gang Wang

    (Fudan University)

  • Bing Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiaohui Jia

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yan Ai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shanshan Chen

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Peilan Tang

    (Chinese Academy of Sciences
    Nanchang University)

  • Aijie Liu

    (Chinese Academy of Sciences)

  • Qianting Yuan

    (Chinese Academy of Sciences)

  • Xin Xie

    (Chinese Academy of Sciences
    ShanghaiTech University
    University of Chinese Academy of Sciences
    Fudan University)

Abstract

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 ~1035 times) 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.

Suggested Citation

  • Ren Guo & Mengmeng Jiang & Gang Wang & Bing Li & Xiaohui Jia & Yan Ai & Shanshan Chen & Peilan Tang & Aijie Liu & Qianting Yuan & Xin Xie, 2022. "IL6 supports long-term expansion of hepatocytes in vitro," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35167-8
    DOI: 10.1038/s41467-022-35167-8
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    References listed on IDEAS

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    1. Andrew W. Duncan & Matthew H. Taylor & Raymond D. Hickey & Amy E. Hanlon Newell & Michelle L. Lenzi & Susan B. Olson & Milton J. Finegold & Markus Grompe, 2010. "The ploidy conveyor of mature hepatocytes as a source of genetic variation," Nature, Nature, vol. 467(7316), pages 707-710, October.
    2. Pengyu Huang & Zhiying He & Shuyi Ji & Huawang Sun & Dao Xiang & Changcheng Liu & Yiping Hu & Xin Wang & Lijian Hui, 2011. "Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors," Nature, Nature, vol. 475(7356), pages 386-389, July.
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    Cited by:

    1. Amrita Goldar & Diya Dasgupta, 2023. "Beyond the Stocktake (Part II): Clean Energy Technologies," Indian Council for Research on International Economic Relations (ICRIER) Policy Paper 14, Indian Council for Research on International Economic Relations (ICRIER), New Delhi, India.
    2. Delilah Hendriks & Benedetta Artegiani & Thanasis Margaritis & Iris Zoutendijk & Susana Chuva de Sousa Lopes & Hans Clevers, 2024. "Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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