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Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner

Stat3 is essential for mouse embryonic stem cell (mESC) self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary “on/off” manner...

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Detalles Bibliográficos
Autores principales: Tai, Chih-I, Schulze, Eric N., Ying, Qi-Long
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197444/
https://www.ncbi.nlm.nih.gov/pubmed/25238758
http://dx.doi.org/10.1242/bio.20149514
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author Tai, Chih-I
Schulze, Eric N.
Ying, Qi-Long
author_facet Tai, Chih-I
Schulze, Eric N.
Ying, Qi-Long
author_sort Tai, Chih-I
collection PubMed
description Stat3 is essential for mouse embryonic stem cell (mESC) self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary “on/off” manner. Here, in contrast to this binary viewpoint, we demonstrate a contextual, rheostat-like mechanism for Stat3's function in mESCs. Activation and expression levels determine whether Stat3 functions in a self-renewal or a differentiation role in mESCs. We also show that Stat3 induces rapid differentiation of mESCs toward the trophectoderm (TE) lineage when its activation level exceeds certain thresholds. Stat3 induces this differentiation phenotype via induction of Tfap2c and its downstream target Cdx2. Our findings provide a novel concept in the realm of Stat3, self-renewal signaling, and pluripotent stem cell biology. Ultimately, this finding may facilitate the development of conditions for the establishment of authentic non-rodent ESCs.
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spelling pubmed-41974442014-10-15 Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner Tai, Chih-I Schulze, Eric N. Ying, Qi-Long Biol Open Research Article Stat3 is essential for mouse embryonic stem cell (mESC) self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary “on/off” manner. Here, in contrast to this binary viewpoint, we demonstrate a contextual, rheostat-like mechanism for Stat3's function in mESCs. Activation and expression levels determine whether Stat3 functions in a self-renewal or a differentiation role in mESCs. We also show that Stat3 induces rapid differentiation of mESCs toward the trophectoderm (TE) lineage when its activation level exceeds certain thresholds. Stat3 induces this differentiation phenotype via induction of Tfap2c and its downstream target Cdx2. Our findings provide a novel concept in the realm of Stat3, self-renewal signaling, and pluripotent stem cell biology. Ultimately, this finding may facilitate the development of conditions for the establishment of authentic non-rodent ESCs. The Company of Biologists 2014-09-19 /pmc/articles/PMC4197444/ /pubmed/25238758 http://dx.doi.org/10.1242/bio.20149514 Text en © 2014. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Tai, Chih-I
Schulze, Eric N.
Ying, Qi-Long
Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
title Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
title_full Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
title_fullStr Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
title_full_unstemmed Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
title_short Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
title_sort stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197444/
https://www.ncbi.nlm.nih.gov/pubmed/25238758
http://dx.doi.org/10.1242/bio.20149514
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