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• W2795314904 startingPage "1667" @default.
• W2795314904 abstract "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." @default.
• W2795314904 created "2018-04-06" @default.
• W2795314904 creator A5003734971 @default.
• W2795314904 creator A5017566265 @default.
• W2795314904 creator A5048898887 @default.
• W2795314904 creator A5052676364 @default.
• W2795314904 creator A5054578405 @default.
• W2795314904 date "2018-03-29" @default.
• W2795314904 modified "2023-10-14" @default.
• W2795314904 title "Lgr5+ intestinal stem cells reside in an unlicensed G1 phase" @default.
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• W2795314904 doi "https://doi.org/10.1083/jcb.201708023" @default.
• W2795314904 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5940300" @default.
• W2795314904 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29599208" @default.
• W2795314904 hasPublicationYear "2018" @default.
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