title: Fibroblast growth factor-10 promotes cardiomyocyte differentiation from embryonic and induced pluripotent stem cells.
abstract: BACKGROUND
  The fibroblast growth factor (FGF) family is essential to normal heart development. Yet, its contribution to cardiomyocyte differentiation from stem cells has not been systemically studied. In this study, we examined the mechanisms and characters of cardiomyocyte differentiation from FGF family protein treated embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.
  
  
  RESULTS
  We used mouse ES cells stably transfected with a cardiac-specific α-myosin heavy chain (αMHC) promoter-driven enhanced green fluorescent protein (EGFP) and mouse iPS cells to investigate cardiomyocyte differentiation. During cardiomyocyte differentiation from mouse ES cells, FGF-3, -8, -10, -11, -13 and -15 showed an expression pattern similar to the mesodermal marker Brachyury and the cardiovascular progenitor marker Flk-1. Among them, FGF-10 induced cardiomyocyte differentiation in a time- and concentration-dependent manner. FGF-10 neutralizing antibody, small molecule FGF receptor antagonist PD173074 and FGF-10 and FGF receptor-2 short hairpin RNAs inhibited cardiomyocyte differentiation. FGF-10 also increased mouse iPS cell differentiation into cardiomyocyte lineage, and this effect was abolished by FGF-10 neutralizing antibody or PD173074. Following Gene Ontology analysis, microarray data indicated that genes involved in cardiac development were upregulated after FGF-10 treatment. In vivo, intramyocardial co-administration of FGF-10 and ES cells demonstrated that FGF-10 also promoted cardiomyocyte differentiation.
  
  
  CONCLUSIONS
  FGF-10 induced cardiomyocyte differentiation from ES cells and iPS cells, which may have potential for translation into clinical applications.
authors.affiliation: Institute of Clinical Medicine and Research Center for Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
authors.forename: Sunny Sun-Kin
authors.initials: SS
authors.lastname: Chan
authors.forename: Hui-Jing
authors.initials: HJ
authors.lastname: Li
authors.forename: Ying-Chang
authors.initials: YC
authors.lastname: Hsueh
authors.forename: Desy S
authors.initials: DS
authors.lastname: Lee
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Chen-Yun
authors.initials: CY
authors.lastname: Chen
authors.forename: Emily
authors.initials: E
authors.lastname: Shih
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D001483:Base Sequence; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D024723:Ventricular Myosins / Q000378:metabolism
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D049452:Green Fluorescent Proteins; D024723:Ventricular Myosins