Identification of Cardiomyocyte-Fated Progenitors from Human-Induced Pluripotent Stem Cells Marked with CD82

  • Takeda, Masafumi
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Kanki, Yasuharu
    Isotope Science Center, The University of Tokyo
  • Masumoto, Hidetoshi
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University・Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine
  • Funakoshi, Shunsuke
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Hatani, Takeshi
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Fukushima, Hiroyuki
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Izumi-Taguchi, Akashi
    Isotope Science Center, The University of Tokyo
  • Matsui, Yusuke
    Division of Systems Biology, Nagoya University Graduate School of Medicine
  • Shimamura, Teppei
    Division of Systems Biology, Nagoya University Graduate School of Medicine
  • Yoshida, Yoshinori
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Yamashita, Jun K.
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University

Description

Here, we find that human-induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM)-fated progenitors (CFPs) that express a tetraspanin family glycoprotein, CD82, almost exclusively differentiate into CMs both in vitro and in vivo. CD82 is transiently expressed in late-stage mesoderm cells during hiPSC differentiation. Purified CD82⁺ cells gave rise to CMs under nonspecific in vitro culture conditions with serum, as well as in vivo after transplantation to the subrenal space or injured hearts in mice, indicating that CD82 successfully marks CFPs. CD82 overexpression in mesoderm cells as well as in undifferentiated hiPSCs increased the secretion of exosomes containing β-catenin and reduced nuclear β-catenin protein, suggesting that CD82 is involved in fated restriction to CMs through Wnt signaling inhibition. This study may contribute to the understanding of CM differentiation mechanisms and to cardiac regeneration strategies.

Journal

  • Cell Reports

    Cell Reports 22 (2), 546-556, 2018-01-09

    Elsevier B.V.

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