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Yes‐associated protein mediates human embryonic stem cell‐derived cardiomyocyte proliferation: Involvement of epidermal growth factor receptor signaling
Author(s) -
Park Somi,
Choe Museog,
Yeo Hancheol,
Han Hojae,
Kim Joongsun,
Chang Woocheol,
Yun Seungpil,
Lee Hojin,
Lee Minyoung
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26625
Subject(s) - protein kinase b , microbiology and biotechnology , mapk/erk pathway , epidermal growth factor , epidermal growth factor receptor , cell growth , embryonic stem cell , phosphorylation , biology , kinase , cell culture , cancer research , receptor , biochemistry , gene , genetics
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.