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

ARIEL WAISMAN; CAMILA VAZQUEZ ECHEGARAY; CLAUDIA SOLARI; MARIA SOLEDAD COSENTINO; IAIN MARTYN; ALESSIA DEGLINCERTI; MOHAMMAD ZEESHAN OZAIR; ALBERT RUZO MATIAS; LINO BARAÑAO; SANTIAGO G. MIRIUKA; ALI BRIVANLOU; ALEJANDRA S. GUBERMAN

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2017

0022-2836

The cell cycle has gained attention as a key determinant for cell fate decisions, but the contribution of DNA replication and mitosis in stem cell differentiation has not been extensively studied. To understand if these processes act as ?windows of opportunity? for changes in cell identity, we established synchronized cultures of mouse embryonic stem cells (mESC) as they exit the ground state of pluripotency. We show that initial transcrip- tional changes in this transition do not require passage through mitosis, and that conver- sion to primed pluripotency is linked to lineage priming in the G1 phase. Importantly, we demonstrate that impairment of DNA replication severely blocks transcriptional switch to primed pluripotency, even in the absence of p53 activity induced by the DNA damage re- sponse. Our data suggest an important role for DNA replication during mESC differentia- tion, which could shed light on why pluripotent cells are only receptive to differentiation signals during G1, that is, before the S-phase.