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HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399227/ https://www.ncbi.nlm.nih.gov/pubmed/25889500 http://dx.doi.org/10.1186/s12967-015-0447-7 |
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author | Sun, Xiaotian Pang, Liewen Shi, Meng Huang, Jiechun Wang, Yiqing |
author_facet | Sun, Xiaotian Pang, Liewen Shi, Meng Huang, Jiechun Wang, Yiqing |
author_sort | Sun, Xiaotian |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0447-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4399227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43992272015-04-17 HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells Sun, Xiaotian Pang, Liewen Shi, Meng Huang, Jiechun Wang, Yiqing J Transl Med Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0447-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-14 /pmc/articles/PMC4399227/ /pubmed/25889500 http://dx.doi.org/10.1186/s12967-015-0447-7 Text en © Sun et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Sun, Xiaotian Pang, Liewen Shi, Meng Huang, Jiechun Wang, Yiqing HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells |
title | HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells |
title_full | HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells |
title_fullStr | HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells |
title_full_unstemmed | HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells |
title_short | HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells |
title_sort | hif2α induces cardiomyogenesis via wnt/β-catenin signaling in mouse embryonic stem cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399227/ https://www.ncbi.nlm.nih.gov/pubmed/25889500 http://dx.doi.org/10.1186/s12967-015-0447-7 |
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