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Human pancreatic beta-like cells converted from fibroblasts

Author

Listed:
  • Saiyong Zhu

    (Gladstone Institute of Cardiovascular Disease, University of California)

  • Holger A. Russ

    (Diabetes Center, University of California, San Francisco)

  • Xiaojing Wang

    (Gladstone Institute of Cardiovascular Disease, University of California)

  • Mingliang Zhang

    (Gladstone Institute of Cardiovascular Disease, University of California)

  • Tianhua Ma

    (Gladstone Institute of Cardiovascular Disease, University of California)

  • Tao Xu

    (Gladstone Institute of Cardiovascular Disease, University of California)

  • Shibing Tang

    (Gladstone Institute of Cardiovascular Disease, University of California)

  • Matthias Hebrok

    (Diabetes Center, University of California, San Francisco)

  • Sheng Ding

    (Gladstone Institute of Cardiovascular Disease, University of California
    University of California San Francisco)

Abstract

Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes.

Suggested Citation

  • Saiyong Zhu & Holger A. Russ & Xiaojing Wang & Mingliang Zhang & Tianhua Ma & Tao Xu & Shibing Tang & Matthias Hebrok & Sheng Ding, 2016. "Human pancreatic beta-like cells converted from fibroblasts," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10080
    DOI: 10.1038/ncomms10080
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    Cited by:

    1. Xiaojie Ma & Jie Cao & Ziyu Zhou & Yunkun Lu & Qin Li & Yan Jin & Guo Chen & Weiyun Wang & Wenyan Ge & Xi Chen & Zhensheng Hu & Xiao Shu & Qian Deng & Jiaqi Pu & Chengzhen Liang & Junfen Fu & Jianzhao, 2022. "N6-methyladenosine modification-mediated mRNA metabolism is essential for human pancreatic lineage specification and islet organogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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