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Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells

The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, and Sox2. The Wnt/β-catenin pathway promotes pluripotency by alleviating T cell...

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Autores principales: Chatterjee, Sujash S., Saj, Abil, Gocha, Tenzin, Murphy, Matthew, Gonsalves, Foster C., Zhang, Xiaoqian, Hayward, Penelope, Akgöl Oksuz, Betül, Shen, Steven S., Madar, Aviv, Martinez Arias, Alfonso, DasGupta, Ramanuj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602028/
https://www.ncbi.nlm.nih.gov/pubmed/26459597
http://dx.doi.org/10.1083/jcb.201503017
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author Chatterjee, Sujash S.
Saj, Abil
Gocha, Tenzin
Murphy, Matthew
Gonsalves, Foster C.
Zhang, Xiaoqian
Hayward, Penelope
Akgöl Oksuz, Betül
Shen, Steven S.
Madar, Aviv
Martinez Arias, Alfonso
DasGupta, Ramanuj
author_facet Chatterjee, Sujash S.
Saj, Abil
Gocha, Tenzin
Murphy, Matthew
Gonsalves, Foster C.
Zhang, Xiaoqian
Hayward, Penelope
Akgöl Oksuz, Betül
Shen, Steven S.
Madar, Aviv
Martinez Arias, Alfonso
DasGupta, Ramanuj
author_sort Chatterjee, Sujash S.
collection PubMed
description The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, and Sox2. The Wnt/β-catenin pathway promotes pluripotency by alleviating T cell factor TCF3-mediated repression of the PTN. However, it has remained unclear how β-catenin’s function as a transcriptional activator with TCF1 influences mESC fate. Here, we show that TCF1-mediated transcription is up-regulated in differentiating mESCs and that chemical inhibition of β-catenin/TCF1 interaction improves long-term self-renewal and enhances functional pluripotency. Genetic loss of TCF1 inhibited differentiation by delaying exit from pluripotency and conferred a transcriptional profile strikingly reminiscent of self-renewing mESCs with high Nanog expression. Together, our data suggest that β-catenin’s function in regulating mESCs is highly context specific and that its interaction with TCF1 promotes differentiation, further highlighting the need for understanding how its individual protein–protein interactions drive stem cell fate.
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spelling pubmed-46020282016-04-12 Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells Chatterjee, Sujash S. Saj, Abil Gocha, Tenzin Murphy, Matthew Gonsalves, Foster C. Zhang, Xiaoqian Hayward, Penelope Akgöl Oksuz, Betül Shen, Steven S. Madar, Aviv Martinez Arias, Alfonso DasGupta, Ramanuj J Cell Biol Research Articles The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, and Sox2. The Wnt/β-catenin pathway promotes pluripotency by alleviating T cell factor TCF3-mediated repression of the PTN. However, it has remained unclear how β-catenin’s function as a transcriptional activator with TCF1 influences mESC fate. Here, we show that TCF1-mediated transcription is up-regulated in differentiating mESCs and that chemical inhibition of β-catenin/TCF1 interaction improves long-term self-renewal and enhances functional pluripotency. Genetic loss of TCF1 inhibited differentiation by delaying exit from pluripotency and conferred a transcriptional profile strikingly reminiscent of self-renewing mESCs with high Nanog expression. Together, our data suggest that β-catenin’s function in regulating mESCs is highly context specific and that its interaction with TCF1 promotes differentiation, further highlighting the need for understanding how its individual protein–protein interactions drive stem cell fate. The Rockefeller University Press 2015-10-12 /pmc/articles/PMC4602028/ /pubmed/26459597 http://dx.doi.org/10.1083/jcb.201503017 Text en © 2015 Chatterjee et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Chatterjee, Sujash S.
Saj, Abil
Gocha, Tenzin
Murphy, Matthew
Gonsalves, Foster C.
Zhang, Xiaoqian
Hayward, Penelope
Akgöl Oksuz, Betül
Shen, Steven S.
Madar, Aviv
Martinez Arias, Alfonso
DasGupta, Ramanuj
Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
title Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
title_full Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
title_fullStr Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
title_full_unstemmed Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
title_short Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
title_sort inhibition of β-catenin–tcf1 interaction delays differentiation of mouse embryonic stem cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602028/
https://www.ncbi.nlm.nih.gov/pubmed/26459597
http://dx.doi.org/10.1083/jcb.201503017
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