Developmental chronology of mouse embryo from 2-cell stage through birth

Current single-cell atlases of mouse embryos are limited in temporal resolution and cellular or sequencing depth coverage. Here we report the mouse developmental Cell and Lineage Atlas (mdCLA), which covers 37 time points across the entire embryonic development from the 2-cell stage (E1.5) to birth (E19.0), with two million cells and a median of 4,500 genes detected per cell. The temporal coverage and data quality of mdCLA surpass the existing mouse embryonic atlases, enabling the identification of organ-specific cell type and gene expression. Using mdCLA, we uncovered divergent gene expression profiles between early and late-stage metanephric progenitor populations, marked by the upregulation of epithelial differentiation and immune response pathways in the late-stage population. Moreover, by analysing the newly generated cell types over time, we revealed an epithelium-specific accelerated differentiation process that occurs after E14.5. The transcription factor upregulated during late developmental stages was validated, where specific ablation of the Tub gene in the pituitary epithelium led to a reduction in the populations producing follicle-stimulating hormone. Consequently, this genetic modification resulted in postnatal obesity in mice. Together, mdCLA offers a comprehensive and high-quality reference, providing critical insights into the dynamic processes and mechanisms underlying mammalian embryogenesis.