G1/S restriction point coordinates phasic gene expression and cell differentiation

Authors

Brian DeVeale, UCSF School of Medicine
Leqian Liu, University of California, San Francisco
Ryan Boileau, UCSF School of Medicine
Jennifer Swindlehurst-Chan, UCSF School of Medicine
Bryan Marsh, UCSF School of Medicine
Jacob W. Freimer, UCSF School of Medicine
Adam Abate, University of California, San Francisco
Robert Blelloch, UCSF School of Medicine

Document Type

Article

Publication Title

Nature Communications

Publication Date

12-1-2022

Volume

13

Issue

1

DOI

10.1038/s41467-022-31101-0

Abstract

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.

E-ISSN

20411723

PubMed ID

35760790

Recommended Citation

DeVeale, Brian; Liu, Leqian; Boileau, Ryan; Swindlehurst-Chan, Jennifer; Marsh, Bryan; Freimer, Jacob W.; Abate, Adam; and Blelloch, Robert. (2022). G1/S restriction point coordinates phasic gene expression and cell differentiation. Nature Communications, 13 (1).
https://scholar.uwindsor.ca/biomedpub/15