title: Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway.
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.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Onizuka
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yuasa
authors.forename: Dai
authors.initials: D
authors.lastname: Kusumoto
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shimoji
authors.forename: Toru
authors.initials: T
authors.lastname: Egashira
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ohno
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kageyama
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Hattori
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
authors.forename: Masaki
authors.initials: M
authors.lastname: Ieda
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kimura
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006321:Heart / Q000196:embryology; D006801:Humans; D020935:MAP Kinase Signaling System; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018808:Transcription Factor AP-1; D051154:Wnt2 Protein