As tissues develop, cells divide and differentiate concurrently. Conflicting evidence shows that cell division is either dispensable or required for formation of cell types. Here, to determine the role of cell division in differentiation, we arrested the cell cycle in zebrafish embryos using two independent approaches and profiled them at single-cell resolution. We show that cell division is dispensable for differentiation of all embryonic tissues from early gastrulation to the end of segmentation. However, arresting cell division does slow down differentiation in some cell types, and it induces global stress responses. While differentiation is robust to blocking cell division, the proportions of cells across cell states are not, but show evidence of partial compensation. This work clarifies our understanding of the role of cell division in development and showcases the utility of combining embryo-wide perturbations with single-cell RNA sequencing to uncover the role of common biological processes across multiple tissues.

随着组织的发育，细胞同时分裂和分化。相互矛盾的证据表明，细胞分裂对于细胞类型的形成要么是可有可无的，要么是必需的。在这里，为了确定细胞分裂在分化中的作用，我们使用两种独立的方法捕获了斑马鱼胚胎中的细胞周期，并以单细胞分辨率对其进行了分析。我们表明，细胞分裂对于从早期原肠胚形成到分割结束的所有胚胎组织的分化是必不可少的。然而，阻止细胞分裂确实会减慢某些细胞类型的分化，并诱导整体应激反应。虽然分化对阻断细胞分裂具有稳健性，但不同细胞状态的细胞比例则不然，但显示出部分补偿的证据。这项工作阐明了我们对细胞分裂在发育中的作用的理解，并展示了将胚胎范围的扰动与单细胞 RNA 测序相结合的效用，以揭示跨多个组织的常见生物过程的作用。