The house mouse is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans. Mouse gestation lasts just three weeks, during which its genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of over 500 million cells. Towards a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing (sci-*) to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2-6 hr intervals spanning late gastrulation (embryonic day 8, E8) to birth (postnatal day 0, P0), From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis, kidney, mesenchyme, retina, and early neurons. We leverage the temporal resolution and sampling depth of these whole embryo snapshots, together with published data from earlier timepoints, to construct a rooted tree of cell type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate transcription factors (TFs) and other genes as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most temporally dramatic shifts in cell states are observed within one hour of birth, and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.

For more details: https://www.nature.com/articles/s41586-024-07069-w