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Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation

Controlling responsiveness to prevailing signals is critical for robust transitions between cell states during development. For example, fibroblast growth factor (FGF) drives naive pluripotent cells into extraembryonic lineages before implantation but sustains pluripotency in primed cells of the pos...

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Detalles Bibliográficos
Autores principales: Malaguti, Mattias, Migueles, Rosa Portero, Blin, Guillaume, Lin, Chia-Yi, Lowell, Sally
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706657/
https://www.ncbi.nlm.nih.gov/pubmed/31204172
http://dx.doi.org/10.1016/j.devcel.2019.05.032
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author Malaguti, Mattias
Migueles, Rosa Portero
Blin, Guillaume
Lin, Chia-Yi
Lowell, Sally
author_facet Malaguti, Mattias
Migueles, Rosa Portero
Blin, Guillaume
Lin, Chia-Yi
Lowell, Sally
author_sort Malaguti, Mattias
collection PubMed
description Controlling responsiveness to prevailing signals is critical for robust transitions between cell states during development. For example, fibroblast growth factor (FGF) drives naive pluripotent cells into extraembryonic lineages before implantation but sustains pluripotency in primed cells of the post-implantation epiblast. Nanog supports pluripotency in naive cells, while Nodal supports pluripotency in primed cells, but the handover from Nanog to Nodal does not proceed seamlessly, opening up the risk of aberrant differentiation if FGF is activated before Nodal. Here, we report that Id1 acts as a sensor to detect delays in Nodal activation after the downregulation of Nanog. Id1 then suppresses FGF activity to delay differentiation. Accordingly, Id1 is not required for naive or primed pluripotency but rather stabilizes epiblast identity during the transition between these states. These findings help explain how development proceeds robustly in the face of imprecise signals and highlight the importance of mechanisms that stabilize cell identity during developmental transitions.
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spelling pubmed-67066572019-08-28 Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation Malaguti, Mattias Migueles, Rosa Portero Blin, Guillaume Lin, Chia-Yi Lowell, Sally Dev Cell Article Controlling responsiveness to prevailing signals is critical for robust transitions between cell states during development. For example, fibroblast growth factor (FGF) drives naive pluripotent cells into extraembryonic lineages before implantation but sustains pluripotency in primed cells of the post-implantation epiblast. Nanog supports pluripotency in naive cells, while Nodal supports pluripotency in primed cells, but the handover from Nanog to Nodal does not proceed seamlessly, opening up the risk of aberrant differentiation if FGF is activated before Nodal. Here, we report that Id1 acts as a sensor to detect delays in Nodal activation after the downregulation of Nanog. Id1 then suppresses FGF activity to delay differentiation. Accordingly, Id1 is not required for naive or primed pluripotency but rather stabilizes epiblast identity during the transition between these states. These findings help explain how development proceeds robustly in the face of imprecise signals and highlight the importance of mechanisms that stabilize cell identity during developmental transitions. Cell Press 2019-08-19 /pmc/articles/PMC6706657/ /pubmed/31204172 http://dx.doi.org/10.1016/j.devcel.2019.05.032 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Malaguti, Mattias
Migueles, Rosa Portero
Blin, Guillaume
Lin, Chia-Yi
Lowell, Sally
Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation
title Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation
title_full Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation
title_fullStr Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation
title_full_unstemmed Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation
title_short Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation
title_sort id1 stabilizes epiblast identity by sensing delays in nodal activation and adjusting the timing of differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706657/
https://www.ncbi.nlm.nih.gov/pubmed/31204172
http://dx.doi.org/10.1016/j.devcel.2019.05.032
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