title: AW551984: a novel regulator of cardiomyogenesis in pluripotent embryonic cells.
abstract: An understanding of the mechanism that regulates the cardiac differentiation of pluripotent stem cells is necessary for the effective generation and expansion of cardiomyocytes as cell therapy products. In the present study, we have identified genes that modulate the cardiac differentiation of pluripotent embryonic cells. We isolated P19CL6 cell sublines that possess distinct properties in cardiomyogenesis and extracted 24 CMR (cardiomyogenesis-related candidate) genes correlated with cardiomyogenesis using a transcriptome analysis. Knockdown of the CMR genes by RNAi (RNA interference) revealed that 18 genes influence spontaneous contraction or transcript levels of cardiac marker genes in EC (embryonal carcinoma) cells. We also performed knockdown of the CMR genes in mouse ES (embryonic stem) cells and induced in vitro cardiac differentiation. Three CMR genes, AW551984, 2810405K02Rik (RIKEN cDNA 2810405K02 gene) and Cd302 (CD302 antigen), modulated the cardiac differentiation of both EC cells and ES cells. Depletion of AW551984 attenuated the expression of the early cardiac transcription factor Nkx2.5 (NK2 transcription factor related locus 5) without affecting transcript levels of pluripotency and early mesoderm marker genes during ES cell differentiation. Activation of Wnt/β-catenin signalling enhanced the expression of both AW551984 and Nkx2.5 in ES cells during embryoid body formation. Our findings indicate that AW551984 is a novel regulator of cardiomyogenesis from pluripotent embryonic cells, which links Wnt/β-catenin signalling to Nkx2.5 expression.
authors.affiliation: Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Hosono
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Satoh
authors.forename: Kei
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kageyoshi
authors.initials: K
authors.lastname: Ono
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Takao
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Teruhide
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology
chemical_list: C560751:AW551984 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins