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

Brian DeVeale, Leqian Liu, Ryan Boileau, Jennifer Swindlehurst-Chan, Bryan Marsh, Jacob W. Freimer, Adam Abate and Robert Blelloch ()
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Brian DeVeale: University of California San Francisco
Leqian Liu: University of California San Francisco
Ryan Boileau: University of California San Francisco
Jennifer Swindlehurst-Chan: University of California San Francisco
Bryan Marsh: University of California San Francisco
Jacob W. Freimer: University of California San Francisco
Adam Abate: University of California San Francisco
Robert Blelloch: University of California San Francisco

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31101-0

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