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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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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. |
format | Online Article Text |
id | pubmed-9237072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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