Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway

Takeshi Onizuka, Shinsuke Yuasa, Dai Kusumoto, Kenichiro Shimoji, Toru Egashira, Yohei Ohno, Toshimi Kageyama, Tomofumi Tanaka, Fumiyuki Hattori, Jun Fujita, Masaki Ieda, Kensuke Kimura, Shinji Makino, Motoaki Sano, Akira Kudo, Keiichi Fukuda

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

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Keywords

  • Cardiomyocyte
  • Embryonic stem cell
  • Induced pluripotent stem cells
  • Mesodermal cells
  • Non-canonical pathway
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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