| First Author | Hwang Y | Year | 2017 |
| Journal | Sci Adv | Volume | 3 |
| Issue | 5 | Pages | e1700298 |
| PubMed ID | 28560351 | Mgi Jnum | J:329138 |
| Mgi Id | MGI:6838200 | Doi | 10.1126/sciadv.1700298 |
| Citation | Hwang Y, et al. (2017) Global increase in replication fork speed during a p57(KIP2)-regulated erythroid cell fate switch. Sci Adv 3(5):e1700298 |
| abstractText | 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 p57(KIP2)-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 p57(KIP2) 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. |
