The epigenetic modifier Fam208a is required to maintain epiblast cell fitness

Abstract Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programm...

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Autores principales:	Shohag Bhargava, Brian Cox, Christiana Polydorou, Veronika Gresakova, Vladimir Korinek, Hynek Strnad, Radislav Sedlacek, Trevor Allan Epp, Kallayanee Chawengsaksophak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a75928153f674212b2fdce97ae6ec453
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spelling	oai:doaj.org-article:a75928153f674212b2fdce97ae6ec4532021-12-02T15:05:41ZThe epigenetic modifier Fam208a is required to maintain epiblast cell fitness10.1038/s41598-017-09490-w2045-2322https://doaj.org/article/a75928153f674212b2fdce97ae6ec4532017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09490-whttps://doaj.org/toc/2045-2322Abstract Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.Shohag BhargavaBrian CoxChristiana PolydorouVeronika GresakovaVladimir KorinekHynek StrnadRadislav SedlacekTrevor Allan EppKallayanee ChawengsaksophakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shohag Bhargava Brian Cox Christiana Polydorou Veronika Gresakova Vladimir Korinek Hynek Strnad Radislav Sedlacek Trevor Allan Epp Kallayanee Chawengsaksophak The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
description	Abstract Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.
format	article
author	Shohag Bhargava Brian Cox Christiana Polydorou Veronika Gresakova Vladimir Korinek Hynek Strnad Radislav Sedlacek Trevor Allan Epp Kallayanee Chawengsaksophak
author_facet	Shohag Bhargava Brian Cox Christiana Polydorou Veronika Gresakova Vladimir Korinek Hynek Strnad Radislav Sedlacek Trevor Allan Epp Kallayanee Chawengsaksophak
author_sort	Shohag Bhargava
title	The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
title_short	The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
title_full	The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
title_fullStr	The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
title_full_unstemmed	The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
title_sort	epigenetic modifier fam208a is required to maintain epiblast cell fitness
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a75928153f674212b2fdce97ae6ec453
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The epigenetic modifier Fam208a is required to maintain epiblast cell fitness

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