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Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs
It has previously been reported that mouse epiblast stem cell (EpiSC) lines comprise heterogeneous cell populations that are functionally equivalent to cells of either early- or late-stage postimplantation development. So far, the establishment of the embryonic stem cell (ESC) pluripotency gene regu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850425/ https://www.ncbi.nlm.nih.gov/pubmed/27149845 http://dx.doi.org/10.1016/j.celrep.2016.03.073 |
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author | Illich, Damir Jacob Zhang, Miao Ursu, Andrei Osorno, Rodrigo Kim, Kee-Pyo Yoon, Juyong Araúzo-Bravo, Marcos J. Wu, Guangming Esch, Daniel Sabour, Davood Colby, Douglas Grassme, Kathrin S. Chen, Jiayu Greber, Boris Höing, Susanne Herzog, Wiebke Ziegler, Slava Chambers, Ian Gao, Shaorong Waldmann, Herbert Schöler, Hans R. |
author_facet | Illich, Damir Jacob Zhang, Miao Ursu, Andrei Osorno, Rodrigo Kim, Kee-Pyo Yoon, Juyong Araúzo-Bravo, Marcos J. Wu, Guangming Esch, Daniel Sabour, Davood Colby, Douglas Grassme, Kathrin S. Chen, Jiayu Greber, Boris Höing, Susanne Herzog, Wiebke Ziegler, Slava Chambers, Ian Gao, Shaorong Waldmann, Herbert Schöler, Hans R. |
author_sort | Illich, Damir Jacob |
collection | PubMed |
description | It has previously been reported that mouse epiblast stem cell (EpiSC) lines comprise heterogeneous cell populations that are functionally equivalent to cells of either early- or late-stage postimplantation development. So far, the establishment of the embryonic stem cell (ESC) pluripotency gene regulatory network through the widely known chemical inhibition of MEK and GSK3beta has been impractical in late-stage EpiSCs. Here, we show that chemical inhibition of casein kinase 1alpha (CK1alpha) induces the conversion of recalcitrant late-stage EpiSCs into ESC pluripotency. CK1alpha inhibition directly results in the simultaneous activation of the WNT signaling pathway, together with inhibition of the TGFbeta/SMAD2 signaling pathway, mediating the rewiring of the gene regulatory network in favor of an ESC-like state. Our findings uncover a molecular mechanism that links CK1alpha to ESC pluripotency through the direct modulation of WNT and TGFbeta signaling. |
format | Online Article Text |
id | pubmed-4850425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48504252016-05-06 Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs Illich, Damir Jacob Zhang, Miao Ursu, Andrei Osorno, Rodrigo Kim, Kee-Pyo Yoon, Juyong Araúzo-Bravo, Marcos J. Wu, Guangming Esch, Daniel Sabour, Davood Colby, Douglas Grassme, Kathrin S. Chen, Jiayu Greber, Boris Höing, Susanne Herzog, Wiebke Ziegler, Slava Chambers, Ian Gao, Shaorong Waldmann, Herbert Schöler, Hans R. Cell Rep Article It has previously been reported that mouse epiblast stem cell (EpiSC) lines comprise heterogeneous cell populations that are functionally equivalent to cells of either early- or late-stage postimplantation development. So far, the establishment of the embryonic stem cell (ESC) pluripotency gene regulatory network through the widely known chemical inhibition of MEK and GSK3beta has been impractical in late-stage EpiSCs. Here, we show that chemical inhibition of casein kinase 1alpha (CK1alpha) induces the conversion of recalcitrant late-stage EpiSCs into ESC pluripotency. CK1alpha inhibition directly results in the simultaneous activation of the WNT signaling pathway, together with inhibition of the TGFbeta/SMAD2 signaling pathway, mediating the rewiring of the gene regulatory network in favor of an ESC-like state. Our findings uncover a molecular mechanism that links CK1alpha to ESC pluripotency through the direct modulation of WNT and TGFbeta signaling. Cell Press 2016-04-14 /pmc/articles/PMC4850425/ /pubmed/27149845 http://dx.doi.org/10.1016/j.celrep.2016.03.073 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Illich, Damir Jacob Zhang, Miao Ursu, Andrei Osorno, Rodrigo Kim, Kee-Pyo Yoon, Juyong Araúzo-Bravo, Marcos J. Wu, Guangming Esch, Daniel Sabour, Davood Colby, Douglas Grassme, Kathrin S. Chen, Jiayu Greber, Boris Höing, Susanne Herzog, Wiebke Ziegler, Slava Chambers, Ian Gao, Shaorong Waldmann, Herbert Schöler, Hans R. Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs |
title | Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs |
title_full | Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs |
title_fullStr | Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs |
title_full_unstemmed | Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs |
title_short | Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs |
title_sort | distinct signaling requirements for the establishment of esc pluripotency in late-stage episcs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850425/ https://www.ncbi.nlm.nih.gov/pubmed/27149845 http://dx.doi.org/10.1016/j.celrep.2016.03.073 |
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