Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows.

胚胎发生需要大量协调才能将遗传程序转化为分化细胞的集体行为，但理解细胞决策如何控制组织形态在概念和技术上仍然具有挑战性。在这里，我们将基于 Cas9 的连续分子记录与基于小鼠胚胎干细胞的胚胎干模型相结合，构建单细胞系统发育，描述瞬时多能神经中胚层祖细胞 (NMP) 在进入神经和中胚层时的行为。体细胞类型。我们发现 NMP 显示出与其最近分化相关的微妙转录特征，并通过令人惊讶的广泛分布的个体命运结果对下游谱系做出贡献。尽管决策可能受到环境因素的严重影响，从而诱发形态表型，但轴向祖细胞本质上会随着发育时间的推移而成熟，以有利于神经谱系。利用这些数据，我们提出了一个实验和分析框架，用于探索瞬时祖细胞群在关键发育窗口期间塑造复杂组织时的非稳态动力学。