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G1/S restriction point coordinates phasic gene expression and cell differentiation

Pluripotent embryonic stem cells have a unique cell cycle structure with a suppressed G1/S restriction point and little differential expression across the cell cycle phases. Here, we evaluate the link between G1/S restriction point activation, phasic gene expression, and cellular differentiation. Ex...

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Autores principales: DeVeale, Brian, Liu, Leqian, Boileau, Ryan, Swindlehurst-Chan, Jennifer, Marsh, Bryan, Freimer, Jacob W., Abate, Adam, Blelloch, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237072/
https://www.ncbi.nlm.nih.gov/pubmed/35760790
http://dx.doi.org/10.1038/s41467-022-31101-0
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author DeVeale, Brian
Liu, Leqian
Boileau, Ryan
Swindlehurst-Chan, Jennifer
Marsh, Bryan
Freimer, Jacob W.
Abate, Adam
Blelloch, Robert
author_facet DeVeale, Brian
Liu, Leqian
Boileau, Ryan
Swindlehurst-Chan, Jennifer
Marsh, Bryan
Freimer, Jacob W.
Abate, Adam
Blelloch, Robert
author_sort DeVeale, Brian
collection PubMed
description Pluripotent embryonic stem cells have a unique cell cycle structure with a suppressed G1/S restriction point and little differential expression across the cell cycle phases. Here, we evaluate the link between G1/S restriction point activation, phasic gene expression, and cellular differentiation. Expression analysis reveals a gain in phasic gene expression across lineages between embryonic days E7.5 and E9.5. Genetic manipulation of the G1/S restriction point regulators miR-302 and P27 respectively accelerates or delays the onset of phasic gene expression in mouse embryos. Loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a constitutive Cyclin E mutant blocks it. Together, these findings uncover a causal relationship between emergence of the G1/S restriction point with a gain in phasic gene expression and cellular differentiation.
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spelling pubmed-92370722022-06-29 G1/S restriction point coordinates phasic gene expression and cell differentiation DeVeale, Brian Liu, Leqian Boileau, Ryan Swindlehurst-Chan, Jennifer Marsh, Bryan Freimer, Jacob W. Abate, Adam Blelloch, Robert Nat Commun Article Pluripotent embryonic stem cells have a unique cell cycle structure with a suppressed G1/S restriction point and little differential expression across the cell cycle phases. Here, we evaluate the link between G1/S restriction point activation, phasic gene expression, and cellular differentiation. Expression analysis reveals a gain in phasic gene expression across lineages between embryonic days E7.5 and E9.5. Genetic manipulation of the G1/S restriction point regulators miR-302 and P27 respectively accelerates or delays the onset of phasic gene expression in mouse embryos. Loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a constitutive Cyclin E mutant blocks it. Together, these findings uncover a causal relationship between emergence of the G1/S restriction point with a gain in phasic gene expression and cellular differentiation. Nature Publishing Group UK 2022-06-27 /pmc/articles/PMC9237072/ /pubmed/35760790 http://dx.doi.org/10.1038/s41467-022-31101-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
DeVeale, Brian
Liu, Leqian
Boileau, Ryan
Swindlehurst-Chan, Jennifer
Marsh, Bryan
Freimer, Jacob W.
Abate, Adam
Blelloch, Robert
G1/S restriction point coordinates phasic gene expression and cell differentiation
title G1/S restriction point coordinates phasic gene expression and cell differentiation
title_full G1/S restriction point coordinates phasic gene expression and cell differentiation
title_fullStr G1/S restriction point coordinates phasic gene expression and cell differentiation
title_full_unstemmed G1/S restriction point coordinates phasic gene expression and cell differentiation
title_short G1/S restriction point coordinates phasic gene expression and cell differentiation
title_sort g1/s restriction point coordinates phasic gene expression and cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237072/
https://www.ncbi.nlm.nih.gov/pubmed/35760790
http://dx.doi.org/10.1038/s41467-022-31101-0
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