Fear of commitment: Hes1 protects quiescent fibroblasts from irreversible cellular fates

Abstract

The cellular state of quiescence is characterized by an exit from the cell cycle that is reversible, that is, upon appropriate stimulation, quiescent cells can re-enter the cell cycle, proliferate and produce progeny.  In this way, quiescent cells can be distinguished from cells in an irreversibly arrested state such as senescence or terminal differentiation.  The molecular basis for reversible versus irreversible cell cycle arrest is unclear.  In a recent study, we demonstrated that the transcriptional regulator Hes1 has a role in maintaining fibroblasts in a reversible quiescent state: overexpression of Hes1 protects fibroblasts against senescence or differentiation, and inhibition of endogenous Hes1 makes quiescent fibroblasts more susceptible to these states.  Here we describe the molecular mechanisms by which Hes1 regulates gene expression by modifying histone tails and thus affecting chromatin conformation.  We put forward models for how Hes1 is regulated and how it protects quiescent cells from differentiation and senescence.