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DNA replication fork speed underlies cell fate changes and promotes reprogramming

Totipotency emerges in early embryogenesis, but its molecular underpinnings remain poorly characterized. In the present study, we employed DNA fiber analysis to investigate how pluripotent stem cells are reprogrammed into totipotent-like 2-cell-like cells (2CLCs). We show that totipotent cells of th...

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Autores principales: Nakatani, Tsunetoshi, Lin, Jiangwei, Ji, Fei, Ettinger, Andreas, Pontabry, Julien, Tokoro, Mikiko, Altamirano-Pacheco, Luis, Fiorentino, Jonathan, Mahammadov, Elmir, Hatano, Yu, Van Rechem, Capucine, Chakraborty, Damayanti, Ruiz-Morales, Elias R., Arguello Pascualli, Paola Y., Scialdone, Antonio, Yamagata, Kazuo, Whetstine, Johnathan R., Sadreyev, Ruslan I., Torres-Padilla, Maria-Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920892/
https://www.ncbi.nlm.nih.gov/pubmed/35256805
http://dx.doi.org/10.1038/s41588-022-01023-0
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author Nakatani, Tsunetoshi
Lin, Jiangwei
Ji, Fei
Ettinger, Andreas
Pontabry, Julien
Tokoro, Mikiko
Altamirano-Pacheco, Luis
Fiorentino, Jonathan
Mahammadov, Elmir
Hatano, Yu
Van Rechem, Capucine
Chakraborty, Damayanti
Ruiz-Morales, Elias R.
Arguello Pascualli, Paola Y.
Scialdone, Antonio
Yamagata, Kazuo
Whetstine, Johnathan R.
Sadreyev, Ruslan I.
Torres-Padilla, Maria-Elena
author_facet Nakatani, Tsunetoshi
Lin, Jiangwei
Ji, Fei
Ettinger, Andreas
Pontabry, Julien
Tokoro, Mikiko
Altamirano-Pacheco, Luis
Fiorentino, Jonathan
Mahammadov, Elmir
Hatano, Yu
Van Rechem, Capucine
Chakraborty, Damayanti
Ruiz-Morales, Elias R.
Arguello Pascualli, Paola Y.
Scialdone, Antonio
Yamagata, Kazuo
Whetstine, Johnathan R.
Sadreyev, Ruslan I.
Torres-Padilla, Maria-Elena
author_sort Nakatani, Tsunetoshi
collection PubMed
description Totipotency emerges in early embryogenesis, but its molecular underpinnings remain poorly characterized. In the present study, we employed DNA fiber analysis to investigate how pluripotent stem cells are reprogrammed into totipotent-like 2-cell-like cells (2CLCs). We show that totipotent cells of the early mouse embryo have slow DNA replication fork speed and that 2CLCs recapitulate this feature, suggesting that fork speed underlies the transition to a totipotent-like state. 2CLCs emerge concomitant with DNA replication and display changes in replication timing (RT), particularly during the early S-phase. RT changes occur prior to 2CLC emergence, suggesting that RT may predispose to gene expression changes and consequent reprogramming of cell fate. Slowing down replication fork speed experimentally induces 2CLCs. In vivo, slowing fork speed improves the reprogramming efficiency of somatic cell nuclear transfer. Our data suggest that fork speed regulates cellular plasticity and that remodeling of replication features leads to changes in cell fate and reprogramming.
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spelling pubmed-89208922022-03-30 DNA replication fork speed underlies cell fate changes and promotes reprogramming Nakatani, Tsunetoshi Lin, Jiangwei Ji, Fei Ettinger, Andreas Pontabry, Julien Tokoro, Mikiko Altamirano-Pacheco, Luis Fiorentino, Jonathan Mahammadov, Elmir Hatano, Yu Van Rechem, Capucine Chakraborty, Damayanti Ruiz-Morales, Elias R. Arguello Pascualli, Paola Y. Scialdone, Antonio Yamagata, Kazuo Whetstine, Johnathan R. Sadreyev, Ruslan I. Torres-Padilla, Maria-Elena Nat Genet Article Totipotency emerges in early embryogenesis, but its molecular underpinnings remain poorly characterized. In the present study, we employed DNA fiber analysis to investigate how pluripotent stem cells are reprogrammed into totipotent-like 2-cell-like cells (2CLCs). We show that totipotent cells of the early mouse embryo have slow DNA replication fork speed and that 2CLCs recapitulate this feature, suggesting that fork speed underlies the transition to a totipotent-like state. 2CLCs emerge concomitant with DNA replication and display changes in replication timing (RT), particularly during the early S-phase. RT changes occur prior to 2CLC emergence, suggesting that RT may predispose to gene expression changes and consequent reprogramming of cell fate. Slowing down replication fork speed experimentally induces 2CLCs. In vivo, slowing fork speed improves the reprogramming efficiency of somatic cell nuclear transfer. Our data suggest that fork speed regulates cellular plasticity and that remodeling of replication features leads to changes in cell fate and reprogramming. Nature Publishing Group US 2022-03-07 2022 /pmc/articles/PMC8920892/ /pubmed/35256805 http://dx.doi.org/10.1038/s41588-022-01023-0 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
Nakatani, Tsunetoshi
Lin, Jiangwei
Ji, Fei
Ettinger, Andreas
Pontabry, Julien
Tokoro, Mikiko
Altamirano-Pacheco, Luis
Fiorentino, Jonathan
Mahammadov, Elmir
Hatano, Yu
Van Rechem, Capucine
Chakraborty, Damayanti
Ruiz-Morales, Elias R.
Arguello Pascualli, Paola Y.
Scialdone, Antonio
Yamagata, Kazuo
Whetstine, Johnathan R.
Sadreyev, Ruslan I.
Torres-Padilla, Maria-Elena
DNA replication fork speed underlies cell fate changes and promotes reprogramming
title DNA replication fork speed underlies cell fate changes and promotes reprogramming
title_full DNA replication fork speed underlies cell fate changes and promotes reprogramming
title_fullStr DNA replication fork speed underlies cell fate changes and promotes reprogramming
title_full_unstemmed DNA replication fork speed underlies cell fate changes and promotes reprogramming
title_short DNA replication fork speed underlies cell fate changes and promotes reprogramming
title_sort dna replication fork speed underlies cell fate changes and promotes reprogramming
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920892/
https://www.ncbi.nlm.nih.gov/pubmed/35256805
http://dx.doi.org/10.1038/s41588-022-01023-0
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