Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions

Hiroyuki Yamakawa, Naoto Muraoka, Kazutaka Miyamoto, Taketaro Sadahiro, Mari Isomi, Sho Haginiwa, Hidenori Kojima, Tomohiko Umei, Mizuha Akiyama, Yuki Kuishi, Junko Kurokawa, Tetsushi Furukawa, Keiichi Fukuda, Masaki Ieda

研究成果: Article査読

96 被引用数 (Scopus)

抄録

Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming.

本文言語English
ページ(範囲)1128-1142
ページ数15
ジャーナルStem cell reports
5
6
DOI
出版ステータスPublished - 2015 12 8

ASJC Scopus subject areas

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

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