A single-cell time-lapse of mouse prenatal development from gastrula to birth. The study presents a comprehensive single-cell transcriptomic analysis of mouse embryos from late gastrulation (embryonic day 8) to birth (postnatal day 0), profiling 12.4 million nuclei from 83 embryos. This dataset provides a detailed temporal resolution of cell-type transitions, revealing the ontogenesis of various tissues, including the posterior embryo during somitogenesis, kidney, mesenchyme, retina, and early neurons. The researchers constructed a rooted tree of cell-type relationships spanning prenatal development, from zygote to birth, and identified candidate genes driving differentiation of hundreds of cell types. The most significant temporal shifts in cell states occur within one hour of birth, likely underpinning the physiological adaptations required for the transition from fetal to postnatal life. The study also highlights the complexity of developmental processes, including the diversification of intermediate mesoderm and lateral plate mesoderm, the emergence of neuronal subtypes from patterned neuroectoderm, and the establishment of lineage relationships among cell types. The findings provide a detailed framework for understanding mammalian development and offer insights into the molecular mechanisms underlying cell-type specification and differentiation. The study also addresses challenges in single-cell analysis, including the heterogeneity of technologies used, the asynchronous nature of transcriptional states with developmental time, and the complexity of the organism. The researchers employed a heuristic approach to construct a rooted tree of cell-type relationships, integrating data from multiple sources and identifying key drivers of cell-type transitions. The study underscores the importance of temporal resolution and sampling depth in understanding developmental processes and highlights the potential for further exploration of this dataset.A single-cell time-lapse of mouse prenatal development from gastrula to birth. The study presents a comprehensive single-cell transcriptomic analysis of mouse embryos from late gastrulation (embryonic day 8) to birth (postnatal day 0), profiling 12.4 million nuclei from 83 embryos. This dataset provides a detailed temporal resolution of cell-type transitions, revealing the ontogenesis of various tissues, including the posterior embryo during somitogenesis, kidney, mesenchyme, retina, and early neurons. The researchers constructed a rooted tree of cell-type relationships spanning prenatal development, from zygote to birth, and identified candidate genes driving differentiation of hundreds of cell types. The most significant temporal shifts in cell states occur within one hour of birth, likely underpinning the physiological adaptations required for the transition from fetal to postnatal life. The study also highlights the complexity of developmental processes, including the diversification of intermediate mesoderm and lateral plate mesoderm, the emergence of neuronal subtypes from patterned neuroectoderm, and the establishment of lineage relationships among cell types. The findings provide a detailed framework for understanding mammalian development and offer insights into the molecular mechanisms underlying cell-type specification and differentiation. The study also addresses challenges in single-cell analysis, including the heterogeneity of technologies used, the asynchronous nature of transcriptional states with developmental time, and the complexity of the organism. The researchers employed a heuristic approach to construct a rooted tree of cell-type relationships, integrating data from multiple sources and identifying key drivers of cell-type transitions. The study underscores the importance of temporal resolution and sampling depth in understanding developmental processes and highlights the potential for further exploration of this dataset.