title: HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells.
abstract: Cardiac cell formation, cardiomyogenesis, is critically dependent on oxygen availability. It is known that hypoxia, a reduced oxygen level, modulates the in vitro differentiation of pluripotent cells into cardiomyocytes via hypoxia inducible factor-1alpha (HIF-1α)-dependent mechanisms. However, the direct impact of HIF-1α deficiency on the formation and maturation of cardiac-like cells derived from mouse embryonic stem cells (mESC) in vitro remains to be elucidated. In the present study, we demonstrated that HIF-1α deficiency significantly altered the quality and quantity of mESC-derived cardiomyocytes. It was accompanied with lower mRNA and protein levels of cardiac cell specific markers (myosin heavy chains 6 and 7) and with a decreasing percentage of myosin heavy chain α and β, and cardiac troponin T-positive cells. As to structural aspects of the differentiated cardiomyocytes, the localization of contractile proteins (cardiac troponin T, myosin heavy chain α and β) and the organization of myofibrils were also different. Simultaneously, HIF-1α deficiency was associated with a lower percentage of beating embryoid bodies. Interestingly, an observed alteration in the in vitro differentiation scheme of HIF-1α deficient cells was accompanied with significantly lower expression of the endodermal marker (hepatic nuclear factor 4 alpha). These findings thus suggest that HIF-1α deficiency attenuates spontaneous cardiomyogenesis through the negative regulation of endoderm development in mESC differentiating in vitro.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.|Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|International Clinical Research Center - Centre of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kudová
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jiřina
authors.initials: J
authors.lastname: Procházková
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.|International Clinical Research Center - Centre of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Vašiček
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.|International Clinical Research Center - Centre of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Perečko
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Sedláčková
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Pešl
authors.affiliation: Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|International Clinical Research Center - Centre of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Pacherník
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.|International Clinical Research Center - Centre of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Lukáš
authors.identifier: http://orcid.org/0000-0002-7729-7338
authors.initials: L
authors.lastname: Kubala
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006321:Heart / Q000196:embryology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D024510:Muscle Development; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D012038:Regeneration; D020107:Troponin T / Q000378:metabolism
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524495:Mlc2a protein, mouse; D018994:Myosin Light Chains; D020107:Troponin T; D000185:Actinin; D018995:Myosin Heavy Chains; D010100:Oxygen