This study presents a comprehensive single-cell transcriptomic time-lapse of mouse prenatal development from gastrula to birth. Using optimized single-cell combinatorial indexing, researchers profiled the transcriptional states of 12.4 million nuclei from 83 embryos, staged at 2- to 6-hour intervals from late gastrulation (embryonic day 8) to birth (postnatal day 0). The data allowed for the annotation of hundreds of cell types and the exploration of ontogenetic processes such as somitogenesis, kidney development, mesenchyme, retina, and early neuron differentiation. The authors constructed a rooted tree of cell-type relationships spanning prenatal development, identifying genes encoding transcription factors and other proteins as candidate drivers of cell differentiation. Notably, the most significant temporal shifts in cell states occurred within one hour of birth, likely underpinning the physiological adaptations necessary for the transition from intrauterine to extrauterine life. The study highlights the importance of rapid changes in gene expression in specific cell types immediately after birth, providing insights into the evolutionary pressures and physiological adaptations required for mammalian development.This study presents a comprehensive single-cell transcriptomic time-lapse of mouse prenatal development from gastrula to birth. Using optimized single-cell combinatorial indexing, researchers profiled the transcriptional states of 12.4 million nuclei from 83 embryos, staged at 2- to 6-hour intervals from late gastrulation (embryonic day 8) to birth (postnatal day 0). The data allowed for the annotation of hundreds of cell types and the exploration of ontogenetic processes such as somitogenesis, kidney development, mesenchyme, retina, and early neuron differentiation. The authors constructed a rooted tree of cell-type relationships spanning prenatal development, identifying genes encoding transcription factors and other proteins as candidate drivers of cell differentiation. Notably, the most significant temporal shifts in cell states occurred within one hour of birth, likely underpinning the physiological adaptations necessary for the transition from intrauterine to extrauterine life. The study highlights the importance of rapid changes in gene expression in specific cell types immediately after birth, providing insights into the evolutionary pressures and physiological adaptations required for mammalian development.