Identification of Cardiomyocyte-Fated Progenitors from Human-Induced Pluripotent Stem Cells Marked with CD82
Masafumi Takeda,
Yasuharu Kanki,
Hidetoshi Masumoto,
Shunsuke Funakoshi,
Takeshi Hatani,
Hiroyuki Fukushima,
Akashi Izumi-Taguchi,
Yusuke Matsui,
Teppei Shimamura,
Yoshinori Yoshida,
Jun K. Yamashita
Affiliations
Masafumi Takeda
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
Yasuharu Kanki
Isotope Science Center, The University of Tokyo, Tokyo 113-0032, Japan
Hidetoshi Masumoto
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Shunsuke Funakoshi
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
Takeshi Hatani
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
Hiroyuki Fukushima
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
Akashi Izumi-Taguchi
Isotope Science Center, The University of Tokyo, Tokyo 113-0032, Japan
Yusuke Matsui
Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Teppei Shimamura
Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Yoshinori Yoshida
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
Jun K. Yamashita
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Corresponding author
Summary: 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. : Takeda et al. find that CD82+ is a cell-surface marker on cardiomyocyte-fated progenitors made from human iPSCs. Keywords: iPSCs, CD82, cardiomyocytes, progenitors, exosome, Wnt inhibition
