Inhibition of cell division and DNA replication impair mouse naïve pluripotency exit

SOLARI C; DEGLINCERTI A; BARAÑAO L; GUBERMAN A; SOLARI C; DEGLINCERTI A; BARAÑAO L; GUBERMAN A; VAZQUEZ ECHEGARAY C; MARTYN I; RUZO MATIAS A; BRIVANLOU A; WAISMAN A; VAZQUEZ ECHEGARAY C; COSENTINO S; MARTYN I; OZAIR M; RUZO MATIAS A; MIRIUKA S; BRIVANLOU A; WAISMAN A; COSENTINO S; OZAIR M; MIRIUKA S

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2017 p. 2802 - 2815

0022-2836

The cell cycle has gained attention as a key determinant forcell fate decisions, but the contribution of DNA replication and mitosisin stem cell differentiation has not been exten-sively studied. Tounderstand if these processes act as ´windows of opportunity´ for changesin cell identity, we established synchronized cultures of mouse embryonicstem cells (mESC) as they exit the ground state of pluripotency. We showthat initial transcriptional changes in this transition do not requirepassage through mitosis, and that conversion to primed pluripo-tency islinked to lineage priming in the G1 phase. Importantly, we demonstratethat impair-ment of DNA replication severely blocks transcriptionalswitch to primed pluripotency, even in the absence of p53 activityinduced by the DNA damage response. Our data suggest an important rolefor DNA replication during mESC differentiation, which could shed lighton why pluripotent cells are only receptive to differentiation signalsduring G1, that is, before the S-phase.