title: HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells.
abstract: BACKGROUND
  Embryonic stem cells (ESCs) are pluripotent stem cells and can differentiate into cardiomyocytes when cultured in appropriate conditions. The function of hypoxia-inducible factors (HIFs) has been identified in directing the formation of cardiac lineages. The purpose of this study was to investigate the ability of HIF2α to induce differentiation of ESCs into cardiomyocytes and to explore the potential underlying molecular mechanisms.
  
  
  METHODS
  Cardiac differentiation from mouse ESCs was analyzed using the "hanging drop" method, and success was determined by assaying the numbers of beating embryoid bodies and the expression level of cardiac markers. The expression of HIF2α was then manipulated during cardiac differentiation with piggyBac transposon and the lentivirus system. The underlying mechanism was finally examined via administering selective inhibitors of the Wnt/β-catenin signaling pathway.
  
  
  RESULTS
  Overexpressing HIF2α can significantly drive mouse ESCs to form cardiomyocytes. Contrarily, knockdown of HIF2α inhibits the emergence of cardiac cells. In addition, the cardiomyogenesis-promoting effect of HIF2α occurred by increasing the protein level of β-catenin, an effector that contributes to cardiac differentiation at an early stage of ESC differentiation.
  
  
  CONCLUSIONS
  HIF2α has a cardiomyogenesis-promoting effect in ESCs via enhancing the activation of the Wnt/β-catenin signaling pathway. Our results may be beneficial for generating and applying cardiomyocytes from ESCs safely and effectively in the future.
authors.affiliation: Department of Cardiothoracic surgery, Huashan Hospital of Fudan University, 12th Wulumuqi Road, Shanghai, 200040, PR, China. xtsun114@126.com.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Cardiothoracic surgery, Huashan Hospital of Fudan University, 12th Wulumuqi Road, Shanghai, 200040, PR, China. lwpang14@163.com.
authors.forename: Liewen
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Cardiothoracic surgery, Huashan Hospital of Fudan University, 12th Wulumuqi Road, Shanghai, 200040, PR, China. mshi89@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Cardiothoracic surgery, Huashan Hospital of Fudan University, 12th Wulumuqi Road, Shanghai, 200040, PR, China. jchhuang1411@126.com.
authors.forename: Jiechun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cardiothoracic surgery, Huashan Hospital of Fudan University, 12th Wulumuqi Road, Shanghai, 200040, PR, China. wangyiqing@huashan.org.cn.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D038081:Organogenesis; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051176:beta Catenin; D000099162:Endothelial PAS Domain-Containing Protein 1