Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.

<h4>Background</h4>Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tanya L Medley, Milena Furtado, Nicholas T Lam, Rejhan Idrizi, David Williams, Paul J Verma, Mauro Costa, David M Kaye
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31b2bbdba9884fb7b07f61bcbf04b3ec
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:31b2bbdba9884fb7b07f61bcbf04b3ec
record_format	dspace
spelling	oai:doaj.org-article:31b2bbdba9884fb7b07f61bcbf04b3ec2021-11-18T08:47:03ZEffect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.1932-620310.1371/journal.pone.0080280https://doaj.org/article/31b2bbdba9884fb7b07f61bcbf04b3ec2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24265804/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes.<h4>Objective</h4>We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process.<h4>Methods</h4>Embryoid bodies (EBs) derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture.<h4>Results</h4>At 14 days of differentiation, 59 ± 2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway.<h4>Conclusion</h4>Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.Tanya L MedleyMilena FurtadoNicholas T LamRejhan IdriziDavid WilliamsPaul J VermaMauro CostaDavid M KayePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80280 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tanya L Medley Milena Furtado Nicholas T Lam Rejhan Idrizi David Williams Paul J Verma Mauro Costa David M Kaye Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.
description	<h4>Background</h4>Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes.<h4>Objective</h4>We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process.<h4>Methods</h4>Embryoid bodies (EBs) derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture.<h4>Results</h4>At 14 days of differentiation, 59 ± 2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway.<h4>Conclusion</h4>Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.
format	article
author	Tanya L Medley Milena Furtado Nicholas T Lam Rejhan Idrizi David Williams Paul J Verma Mauro Costa David M Kaye
author_facet	Tanya L Medley Milena Furtado Nicholas T Lam Rejhan Idrizi David Williams Paul J Verma Mauro Costa David M Kaye
author_sort	Tanya L Medley
title	Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.
title_short	Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.
title_full	Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.
title_fullStr	Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.
title_full_unstemmed	Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.
title_sort	effect of oxygen on cardiac differentiation in mouse ips cells: role of hypoxia inducible factor-1 and wnt/beta-catenin signaling.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/31b2bbdba9884fb7b07f61bcbf04b3ec
work_keys_str_mv	AT tanyalmedley effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT milenafurtado effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT nicholastlam effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT rejhanidrizi effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT davidwilliams effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT pauljverma effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT maurocosta effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling AT davidmkaye effectofoxygenoncardiacdifferentiationinmouseipscellsroleofhypoxiainduciblefactor1andwntbetacateninsignaling
_version_	1718421313659338752

Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.

Ejemplares similares