Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast

Embryonic (ES) and trophoblast (TS) stem cells reflect the first, irrevocable cell fate decision in development that is reinforced by distinct epigenetic lineage barriers. Nonetheless, ES cells can seemingly acquire TS-like characteristics upon manipulation of lineage-determining transcription facto...

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Main Authors:	Cambuli, Francesco, Murray, Alexander, Dean, Wendy, Dudzinska, Dominika, Krueger, Felix, Andrews, Simon, Senner, Claire E., Cook, Simon J., Hemberger, Myriam
Format:	Online
Language:	English
Published:	Nature Pub. Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263130/

id	pubmed-4263130
recordtype	oai_dc
spelling	pubmed-42631302014-12-16 Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast Cambuli, Francesco Murray, Alexander Dean, Wendy Dudzinska, Dominika Krueger, Felix Andrews, Simon Senner, Claire E. Cook, Simon J. Hemberger, Myriam Article Embryonic (ES) and trophoblast (TS) stem cells reflect the first, irrevocable cell fate decision in development that is reinforced by distinct epigenetic lineage barriers. Nonetheless, ES cells can seemingly acquire TS-like characteristics upon manipulation of lineage-determining transcription factors or activation of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway. Here we have interrogated the progression of reprogramming in ES cell models with regulatable Oct4 and Cdx2 transgenes or conditional Erk1/2 activation. Although trans-differentiation into TS-like cells is initiated, lineage conversion remains incomplete in all models, underpinned by the failure to demethylate a small group of TS cell genes. Forced expression of these non-reprogrammed genes improves trans-differentiation efficiency, but still fails to confer a stable TS cell phenotype. Thus, even ES cells in ground-state pluripotency cannot fully overcome the boundaries that separate the first cell lineages but retain an epigenetic memory of their ES cell origin. Nature Pub. Group 2014-11-26 /pmc/articles/PMC4263130/ /pubmed/25423963 http://dx.doi.org/10.1038/ncomms6538 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cambuli, Francesco Murray, Alexander Dean, Wendy Dudzinska, Dominika Krueger, Felix Andrews, Simon Senner, Claire E. Cook, Simon J. Hemberger, Myriam
spellingShingle	Cambuli, Francesco Murray, Alexander Dean, Wendy Dudzinska, Dominika Krueger, Felix Andrews, Simon Senner, Claire E. Cook, Simon J. Hemberger, Myriam Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast
author_facet	Cambuli, Francesco Murray, Alexander Dean, Wendy Dudzinska, Dominika Krueger, Felix Andrews, Simon Senner, Claire E. Cook, Simon J. Hemberger, Myriam
author_sort	Cambuli, Francesco
title	Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast
title_short	Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast
title_full	Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast
title_fullStr	Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast
title_full_unstemmed	Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast
title_sort	epigenetic memory of the first cell fate decision prevents complete es cell reprogramming into trophoblast
description	Embryonic (ES) and trophoblast (TS) stem cells reflect the first, irrevocable cell fate decision in development that is reinforced by distinct epigenetic lineage barriers. Nonetheless, ES cells can seemingly acquire TS-like characteristics upon manipulation of lineage-determining transcription factors or activation of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway. Here we have interrogated the progression of reprogramming in ES cell models with regulatable Oct4 and Cdx2 transgenes or conditional Erk1/2 activation. Although trans-differentiation into TS-like cells is initiated, lineage conversion remains incomplete in all models, underpinned by the failure to demethylate a small group of TS cell genes. Forced expression of these non-reprogrammed genes improves trans-differentiation efficiency, but still fails to confer a stable TS cell phenotype. Thus, even ES cells in ground-state pluripotency cannot fully overcome the boundaries that separate the first cell lineages but retain an epigenetic memory of their ES cell origin.
publisher	Nature Pub. Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263130/
_version_	1613166434021539840

Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast

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