Cell state transitions are decoupled from cell division during early embryo development

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. Kukreja et al. show that blocking cell division in zebrafish does not affect differentiation of major cell types during gastrulation and segmentation, but it does decelerate differentiation of particular cell types and skews their proportions.