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Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells

Authors: Xiaotian Sun, Liewen Pang, Meng Shi, Jiechun Huang, Yiqing Wang

Published in: Journal of Translational Medicine | Issue 1/2015

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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.

Conclusion

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.
Appendix
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Metadata
Title
HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells
Authors
Xiaotian Sun
Liewen Pang
Meng Shi
Jiechun Huang
Yiqing Wang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0447-7

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