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Journal of cellular physiology v.233 no.10, 2018년, pp.7016 - 7025  

Yes‐associated protein mediates human embryonic stem cell‐derived cardiomyocyte proliferation: Involvement of epidermal growth factor receptor signaling

Park, Somi    (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Kore  ); Choe, Museog    (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Kore  ); Yeo, Hancheol    (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Kore  ); Han, Hojae    (College of Veterinary Medicine, Seoul National University, Seoul, South Kore  ); Kim, Joongsun    (K‐herb Research Center, Korea Institute of Oriental Medicine, Daejeon, South Kore  ); Chang, Woocheol    (Department of Biology Education, College of Education, Pusan National University, Busan, South Kore  ); Yun, Seungpil    (Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Marylan  ); Lee, Hojin   Lee, Minyoung  
  • 초록  

    Unlike mature cardiomyocytes, human pluripotent stem cell‐derived cardiomyocytes exhibit higher proliferative capacity; however, the underlying mechanisms involved are yet to be elucidated. Here, we revealed that the Yes‐associated protein (YAP) plays a critical role in regulating cell proliferation in association with epidermal growth factor receptor (EGFR) in human embryonic stem cell‐derived cardiomyocytes (hESC‐CMs). Our results show that low‐density culture significantly promotes the proliferation of hESC‐CMs via YAP. Interestingly, the low‐density culture‐induced YAP expression further induced EGFR expression, without any alterations in the activity of EGFR and its two major downstream kinases, ERK, and AKT. However, treatment of a low‐density‐culture of hESC‐CMs with epidermal growth factor (EGF) increased proliferation via phosphorylation of EGFR, ERK, and AKT, and the EGF‐induced phosphorylation of EGFR, ERK, and AKT was significantly higher in low‐density hESC‐CMs than in high‐density hESC‐CMs. Furthermore, the EGF‐induced activation of EGFR, ERK, and AKT increased YAP expression and subsequently proliferation. In conclusion, YAP mediates both low‐density culture‐induced and EGF‐induced proliferation of hESC‐CMs in low‐density culture conditions.


  • 주제어

    epidermal growth factor receptor .   human embryonic stem cell‐derived cardiomyocytes .   lowdensity culture .   proliferation .   yes‐associated protein.  

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