Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm

Abstract We identified a human embryonic stem cell subline that fails to respond to the differentiation cues needed to obtain endoderm derivatives, differentiating instead into extra-embryonic mesoderm. RNA-sequencing analysis showed that the subline has hyperactivation of the WNT and BMP4 signallin...

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Autores principales:	C. Markouli, E. Couvreu De Deckersberg, D. Dziedzicka, M. Regin, S. Franck, A. Keller, A. Gheldof, M. Geens, K. Sermon, C. Spits
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5397d68c03954269819a8af9ebc46823
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spelling	oai:doaj.org-article:5397d68c03954269819a8af9ebc468232021-12-02T18:03:15ZSustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm10.1038/s41598-021-87547-72045-2322https://doaj.org/article/5397d68c03954269819a8af9ebc468232021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87547-7https://doaj.org/toc/2045-2322Abstract We identified a human embryonic stem cell subline that fails to respond to the differentiation cues needed to obtain endoderm derivatives, differentiating instead into extra-embryonic mesoderm. RNA-sequencing analysis showed that the subline has hyperactivation of the WNT and BMP4 signalling. Modulation of these pathways with small molecules confirmed them as the cause of the differentiation impairment. While activation of WNT and BMP4 in control cells resulted in a loss of endoderm differentiation and induction of extra-embryonic mesoderm markers, inhibition of these pathways in the subline restored its ability to differentiate. Karyotyping and exome sequencing analysis did not identify any changes in the genome that could account for the pathway deregulation. These findings add to the increasing evidence that different responses of stem cell lines to differentiation protocols are based on genetic and epigenetic factors, inherent to the line or acquired during cell culture.C. MarkouliE. Couvreu De DeckersbergD. DziedzickaM. ReginS. FranckA. KellerA. GheldofM. GeensK. SermonC. SpitsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q C. Markouli E. Couvreu De Deckersberg D. Dziedzicka M. Regin S. Franck A. Keller A. Gheldof M. Geens K. Sermon C. Spits Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
description	Abstract We identified a human embryonic stem cell subline that fails to respond to the differentiation cues needed to obtain endoderm derivatives, differentiating instead into extra-embryonic mesoderm. RNA-sequencing analysis showed that the subline has hyperactivation of the WNT and BMP4 signalling. Modulation of these pathways with small molecules confirmed them as the cause of the differentiation impairment. While activation of WNT and BMP4 in control cells resulted in a loss of endoderm differentiation and induction of extra-embryonic mesoderm markers, inhibition of these pathways in the subline restored its ability to differentiate. Karyotyping and exome sequencing analysis did not identify any changes in the genome that could account for the pathway deregulation. These findings add to the increasing evidence that different responses of stem cell lines to differentiation protocols are based on genetic and epigenetic factors, inherent to the line or acquired during cell culture.
format	article
author	C. Markouli E. Couvreu De Deckersberg D. Dziedzicka M. Regin S. Franck A. Keller A. Gheldof M. Geens K. Sermon C. Spits
author_facet	C. Markouli E. Couvreu De Deckersberg D. Dziedzicka M. Regin S. Franck A. Keller A. Gheldof M. Geens K. Sermon C. Spits
author_sort	C. Markouli
title	Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
title_short	Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
title_full	Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
title_fullStr	Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
title_full_unstemmed	Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
title_sort	sustained intrinsic wnt and bmp4 activation impairs hesc differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5397d68c03954269819a8af9ebc46823
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Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm

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