title: Efficient Differentiation of TBX18+/WT1+Epicardial-Like Cells from Human Pluripotent Stem Cells Using Small Molecular Compounds.
abstract: The epicardium promotes neovascularization and cardiomyocyte regeneration by generating vascular smooth muscle cells (SMCs) and producing regenerative factors after adult heart infarction. It is therefore a potential cell resource for repair of the injured heart. However, the epicardium also participates in fibrosis and scarring of the injured heart, complicating its use in regenerative medicine. In this study, we report coexpression of TBX18 and WT1 in the majority of epicardial cells during mouse embryonic epicardial development. Furthermore, we describe a convenient chemically defined, immunogen-free, small molecule-based method for generating TBX18+/WT1+epicardial-like cell populations with 80% homogeneity from human pluripotent stem cells by modulation of the WNT and retinoic acid signaling pathways. These epicardial-like cells exhibited characteristic epicardial cell morphology following passaging and differentiation into functional SMCs or cardiac fibroblast-like cells. Our findings add to existing understanding of human epicardial development and provide an efficient and stable method for generating both human epicardial-like cells and SMCs.
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 Medical School of University of Chinese Academy of Sciences , Beijing, China .
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 Medical School of University of Chinese Academy of Sciences , Beijing, China .
authors.forename: Henghua
authors.initials: H
authors.lastname: Cao
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 Medical School of University of Chinese Academy of Sciences , Beijing, China .
authors.forename: Luyang
authors.initials: L
authors.lastname: Tian
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 Medical School of University of Chinese Academy of Sciences , Beijing, China .
authors.forename: Weibang
authors.initials: W
authors.lastname: Huo
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .
authors.forename: Kui
authors.initials: K
authors.lastname: Zhai
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 Medical School of University of Chinese Academy of Sciences , Beijing, China .
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010496:Pericardium / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D012097:Repressor Proteins / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C523796:Tbx18 protein, human; C420983:Tbx18 protein, mouse; D025721:WT1 Proteins; C583751:WT1 protein, human; C000602896:WT1 protein, mouse
keywords: RA; WNT; epicardial cell; human pluripotent stem cell; smooth muscle cell