Hwang, YungFutran, MelindaHidalgo, DanielPop, RamonaIyer, Divya RamalingamScully, RalphRhind, NicholasSocolovsky, Merav2017-06-152017Hwang, Yung, Melinda Futran, Daniel Hidalgo, Ramona Pop, Divya Ramalingam Iyer, Ralph Scully, Nicholas Rhind, and Merav Socolovsky. 2017. “Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch.” Science Advances 3 (5): e1700298. doi:10.1126/sciadv.1700298. http://dx.doi.org/10.1126/sciadv.1700298.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029731Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase–dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions.en-USSciAdv r-articlesCell Cyclecell cycleCDK inhibitorsreplicationdifferentiationcell fate decisionself renewalerythropoiesishematopoiesisJournal Article2017-06-1510.1126/sciadv.1700298