J 2016

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

KUDOVÁ, Jana, Jiřina PROCHÁZKOVÁ, Ondřej VAŠIČEK, Tomáš PEREČKO, Miroslava SEDLÁČKOVÁ et. al.

Basic information

Original name

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

Authors

KUDOVÁ, Jana (203 Czech Republic, belonging to the institution), Jiřina PROCHÁZKOVÁ (203 Czech Republic, belonging to the institution), Ondřej VAŠIČEK (203 Czech Republic), Tomáš PEREČKO (203 Czech Republic), Miroslava SEDLÁČKOVÁ (203 Czech Republic, belonging to the institution), Martin PEŠL (203 Czech Republic, belonging to the institution), Jiří PACHERNÍK (203 Czech Republic, belonging to the institution) and Lukáš KUBALA (203 Czech Republic)

Edition

Plos one, San Francisco, Public Library of Science, 2016, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.806

RIV identification code

RIV/00216224:14110/16:00088134

Organization unit

Faculty of Medicine

UT WoS

000378859400053

Keywords in English

INDUCIBLE FACTOR 1-ALPHA; GENE-EXPRESSION; CARDIAC DIFFERENTIATION; HIF-1-ALPHA; HEART; CARDIOMYOCYTES; MORPHOGENESIS; ENDODERM; ANGIOGENESIS; HIF-2-ALPHA

Tags

Tags

International impact, Reviewed
Změněno: 12/9/2016 09:56, Ing. Mgr. Věra Pospíšilíková

Abstract

V originále

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.

Links

EE2.3.20.0185, research and development project
Name: Centrum analýz a modelování tkání a orgánů
GJ15-13443Y, research and development project
Name: Úloha hypoxií indukovaného faktoru 1 alfa ve vývoji populace neurálních kmenových buněk myši
Investor: Czech Science Foundation