Despite the noisy nature of single cells, multicellular organisms robustly generate different cell types from one zygote. This process involves dynamic cross regulation between signaling and gene expression that is difficult to capture with fixed-cell approaches. To study signaling dynamics and fate specification during preimplantation development, we generated a transgenic mouse expressing the ERK kinase translocation reporter and measured ERK activity in single cells of live embryos. Our results show primarily active ERK in both the inner cell mass and trophectoderm cells due to fibroblast growth factor (FGF) signaling. Strikingly, a subset of mitotic events results in a short pulse of ERK inactivity in both daughter cells that correlates with elevated endpoint NANOG levels. Moreover, endogenous tagging of Nanog in embryonic stem cells reveals that ERK inhibition promotes enhanced stabilization of NANOG protein after mitosis. Our data show that cell cycle, signaling, and differentiation are coordinated during preimplantation development.

尽管单细胞具有嘈杂的性质，但多细胞生物可以从一个受精卵中产生不同的细胞类型。这个过程涉及信号和基因表达之间的动态交叉调节，而固定细胞方法很难捕捉到这一点。为了研究植入前发育过程中的信号动力学和命运规范，我们生成了表达 ERK 激酶易位报告基因的转基因小鼠，并测量了活胚胎单细胞中的 ERK 活性。我们的结果表明，由于成纤维细胞生长因子 (FGF) 信号传导，在内细胞团和滋养外胚层细胞中主要是活跃的 ERK。引人注目的是，有丝分裂事件的一个子集导致两个子细胞中的 ERK 不活动的短脉冲，这与终点 NANOG 水平升高相关。此外，Nanog 的内源性标记胚胎干细胞中的 ERK 抑制促进了有丝分裂后 NANOG 蛋白的稳定性增强。我们的数据显示细胞周期、信号传导和分化在植入前发育过程中是协调的。