{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nakatani T"],"funding":["MEXT | Japan Society for the Promotion of Science","Deutsche Forschungsgemeinschaft","NIDDK NIH HHS","Helmholtz Association","NCI NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health","NIGMS NIH HHS"],"pagination":["318-327"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8920892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["54(3)"],"pubmed_abstract":["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."],"journal":["Nature genetics"],"pubmed_title":["DNA replication fork speed underlies cell fate changes and promotes reprogramming."],"pmcid":["PMC8920892"],"funding_grant_id":["R01GM097360","CRC 1064","JP18H05528","P30 CA006927","P30 DK040561","R35 GM144131","n.a.","R01 GM097360"],"pubmed_authors":["Nakatani T","Van Rechem C","Mahammadov E","Scialdone A","Pontabry J","Ji F","Sadreyev RI","Torres-Padilla ME","Ruiz-Morales ER","Fiorentino J","Hatano Y","Yamagata K","Whetstine JR","Altamirano-Pacheco L","Chakraborty D","Tokoro M","Lin J","Arguello Pascualli PY","Ettinger A"],"additional_accession":[]},"is_claimable":false,"name":"DNA replication fork speed underlies cell fate changes and promotes reprogramming.","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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-10T00:57:19.447Z","creation":"2025-04-07T01:54:54.081Z"},"accession":"S-EPMC8920892","cross_references":{"pubmed":["35256805"],"doi":["10.1038/s41588-022-01023-0"]}}