Characterization and reduction of non-endocrine cells accompanying islet-like endocrine cells differentiated from human iPSC

HANDLE Open Access
  • Hiyoshi, Hideyuki
    T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)
  • Sakuma, Kensuke
    T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA); Orizuru Therapeutics, Inc
  • Tsubooka-Yamazoe, Noriko
    T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA); Orizuru Therapeutics, Inc
  • Asano, Shinya
    Axcelead Drug Discovery Partners, Inc
  • Mochida, Taisuke
    T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)
  • Yamaura, Junji
    Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA); Pharmaceutical Science, Takeda Pharmaceutical Company Limited
  • Konagaya, Shuhei
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA); Orizuru Therapeutics, Inc
  • Fujii, Ryo
    Axcelead Drug Discovery Partners, Inc
  • Matsumoto, Hirokazu
    T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)
  • Ito, Ryo
    T-CiRA Discovery, Research, Takeda Pharmaceutical Company Limited; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA); Orizuru Therapeutics, Inc
  • Toyoda, Taro
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University; Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)

Abstract

The differentiation of pancreatic endocrine cells from human pluripotent stem cells has been thoroughly investigated for their application in cell therapy against diabetes. Although non-endocrine cells are inevitable contaminating by-products of the differentiation process, a comprehensive profile of such cells is lacking. Therefore, we characterized non-endocrine cells in iPSC-derived pancreatic islet cells (iPIC) using single-cell transcriptomic analysis. We found that non-endocrine cells consist of (1) heterogeneous proliferating cells, and (2) cells with not only pancreatic traits but also liver or intestinal traits marked by FGB or AGR2. Non-endocrine cells specifically expressed FGFR2, PLK1, and LDHB. We demonstrated that inhibition of pathways involving these genes selectively reduced the number of non-endocrine cells in the differentiation process. These findings provide useful insights into cell purification approaches and contribute to the improvement of the mass production of endocrine cells for stem cell-derived cell therapy for diabetes.

Elimination of non-target cells mixed into islet-like cells generated from human iPS cells based on characterization. 京都大学プレスリリース. 2022-04-15.

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Keywords

Details 詳細情報について

  • CRID
    1050010457772484224
  • ISSN
    20452322
  • HANDLE
    2433/269448
  • Text Lang
    en
  • Article Type
    journal article
  • Data Source
    • IRDB

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