Complete and robust human genome duplication requires loading MCM helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but G1 length varies widely among cell types. Using quantitative single cell analyses we found that pluripotent stem cells with naturally short G1 phases load MCM much faster than their isogenic differentiated counterparts with long G1 phases. During the earliest stages of differentiation towards all lineages, MCM loading slows concurrently with G1 lengthening, revealing developmental control of MCM loading. In contrast, ectopic Cyclin E overproduction uncouples short G1 from fast MCM loading. Rapid licensing in stem cells is caused by accumulation of the MCM loading protein, Cdt1. Prematurely slowing MCM loading in pluripotent cells not only lengthens G1 but also accelerates differentiation. Thus, rapid origin licensing is an intrinsic characteristic of stem cells that contributes to pluripotency maintenance.

完整而强大的人类基因组复制需要在许多DNA复制起点处加载MCM解旋酶复合物，这是称为起点许可的必不可少的过程。许可仅限于细胞周期的G1期，但G1长度在细胞类型之间差异很大。使用定量单细胞分析，我们发现具有自然短G1期的多能干细胞加载MCM的速度要快于具有长G1期的同基因分化的对应细胞。在向所有谱系分化的最早阶段，MCM加载会随着G1延长而减慢，从而揭示了MCM加载的发育控制。相反，异位细胞周期蛋白E的过量生产将短的G1与快速的MCM加载解耦。干细胞中的快速许可是由MCM加载蛋白Cdt1的积累引起的。过早减慢多能细胞中MCM的加载不仅延长了G1，而且还加速了分化。因此，快速起源许可是干细胞的固有特征，有助于维持多能性。