Distinct Cell-Cycle Control in Two Different States of Mouse Pluripotency

Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Menno ter Huurne, James Chappell, Stephen Dalton, Hendrik G. Stunnenberg
Mouse embryonic stem cells (ESCs) cultured in serum are characterized by hyper-phosphorylated RB protein, lack of G1 control, and rapid progression through the cell cycle. Here, we show that ESCs grown in the presence of two small-molecule inhibitors (2i ESCs) have a longer G1-phase with hypo-phosphorylated RB, implying that they have a functional G1 checkpoint. Deletion of RB, P107, and P130 in 2i ESCs results in a G1-phase similar to that of serum ESCs. Inhibition of the ERK signaling pathway in serum ESCs results in the appearance of hypo-phosphorylated RB and the reinstatement of a G1 checkpoint. In addition, induction of a dormant state by the inhibition of MYC, resembling diapause, requires the presence of the RB family proteins. Collectively, our data show that RB-dependent G1 restriction point signaling is active in mouse ESCs grown in 2i but abrogated in serum by ERK-dependent phosphorylation.

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Teaser

It is widely thought that embryonic stem cells have an unusual and very rapid cell cycle, lacking normal G1 regulation. Stunnenberg and colleagues show that, in mouse ESCs, G1 regulation is, in fact, intact but abrogated in serum by ERK signaling and RB phosphorylation.


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