HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells

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Authors

KUDOVÁ Jana PROCHÁZKOVÁ Jiřina VAŠIČEK Ondřej PEREČKO Tomáš SEDLÁČKOVÁ Miroslava PEŠL Martin PACHERNÍK Jiří KUBALA Lukáš

Year of publication 2016
Type Article in Periodical
Magazine / Source Plos one
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1371/journal.pone.0158358
Field Genetics and molecular biology
Keywords INDUCIBLE FACTOR 1-ALPHA; GENE-EXPRESSION; CARDIAC DIFFERENTIATION; HIF-1-ALPHA; HEART; CARDIOMYOCYTES; MORPHOGENESIS; ENDODERM; ANGIOGENESIS; HIF-2-ALPHA
Description 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-1 alpha)-dependent mechanisms. However, the direct impact of HIF-1 alpha 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-1 alpha 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 alpha and beta, 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 alpha and beta) and the organization of myofibrils were also different. Simultaneously, HIF-1 alpha deficiency was associated with a lower percentage of beating embryoid bodies. Interestingly, an observed alteration in the in vitro differentiation scheme of HIF-1 alpha deficient cells was accompanied with significantly lower expression of the endodermal marker (hepatic nuclear factor 4 alpha). These findings thus suggest that HIF-1 alpha deficiency attenuates spontaneous cardiomyogenesis through the negative regulation of endoderm development in mESC differentiating in vitro.
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