Mouse embryonic development is a canonical model system for studying mammalian cell fate acquisition. Recently, single-cell atlases comprehensively charted embryonic transcriptional landscapes, yet inference of the coordinated dynamics of cells over such atlases remains challenging. Here, we introduce a temporal model for mouse gastrulation, consisting of data from 153 individually sampled embryos spanning 36 h of molecular diversification. Using algorithms and precise timing, we infer differentiation flows and lineage specification dynamics over the embryonic transcriptional manifold. Rapid transcriptional bifurcations characterize the commitment of early specialized node and blood cells. However, for most lineages, we observe combinatorial multi-furcation dynamics rather than hierarchical transcriptional transitions. In the mesoderm, dozens of transcription factors combinatorially regulate multifurcations, as we exemplify using time-matched chimeric embryos of Foxc1/Foxc2 mutants. Our study rejects the notion of differentiation being governed by a series of binary choices, providing an alternative quantitative model for cell fate acquisition.

小鼠胚胎发育是研究哺乳动物细胞命运获得的典型模型系统。最近，单细胞图谱全面绘制了胚胎转录图谱，但推断细胞在此类图谱上的协调动力学仍然具有挑战性。在这里，我们引入了小鼠原肠胚形成的时间模型，该模型由跨越 36 小时分子多样化的 153 个单独采样胚胎的数据组成。使用算法和精确的时间，我们推断胚胎转录流形上的分化流和谱系规范动态。快速转录分叉表征了早期特化节点和血细胞的承诺。然而，对于大多数谱系，我们观察到组合多分叉动力学而不是层次转录转变。在中胚层，正如我们使用 Foxc1/Foxc2 突变体的时间匹配嵌合胚胎举例说明的那样，数十种转录因子组合调节多分叉。我们的研究拒绝了由一系列二元选择控制的分化概念，为细胞命运获取提供了另一种定量模型。