| First Author | Carroll TD | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 5 | Pages | 1667-1685 |
| PubMed ID | 29599208 | Mgi Jnum | J:261429 |
| Mgi Id | MGI:6155420 | Doi | 10.1083/jcb.201708023 |
| Citation | Carroll TD, et al. (2018) Lgr5(+) intestinal stem cells reside in an unlicensed G1 phase. J Cell Biol 217(5):1667-1685 |
| abstractText | During late mitosis and the early G1 phase, the origins of replication are licensed by binding to double hexamers of MCM2-7. In this study, we investigated how licensing and proliferative commitment are coupled in the epithelium of the small intestine. We developed a method for identifying cells in intact tissue containing DNA-bound MCM2-7. Interphase cells above the transit-amplifying compartment had no DNA-bound MCM2-7, but still expressed the MCM2-7 protein, suggesting that licensing is inhibited immediately upon differentiation. Strikingly, we found most proliferative Lgr5(+) stem cells are in an unlicensed state. This suggests that the elongated cell-cycle of intestinal stem cells is caused by an increased G1 length, characterized by dormant periods with unlicensed origins. Significantly, the unlicensed state is lost in Apc-mutant epithelium, which lacks a functional restriction point, causing licensing immediately upon G1 entry. We propose that the unlicensed G1 phase of intestinal stem cells creates a temporal window when proliferative fate decisions can be made. |
