Department of Molecular, Cell and Cancer Biology; Department of Biochemistry and Molecular Pharmacology
Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology
Cell 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.
CDK inhibitors, cell cycle, cell fate decision, differentiation, erythropoiesis, hematopoiesis, replication, self renewal
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2017 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
DOI of Published Version
Sci Adv. 2017 May 26;3(5):e1700298. doi: 10.1126/sciadv.1700298. eCollection 2017 May. Link to article on publisher's site
Hwang Y, Futran M, Hidalgo D, Pop R, Iyer DR, Scully R, Rhind NR, Socolovsky M. (2017). Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch. Open Access Publications by UMMS Authors. https://doi.org/10.1126/sciadv.1700298. Retrieved from https://escholarship.umassmed.edu/oapubs/3152
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