A single-cell time-lapse of mouse prenatal development from gastrula to birth

• 成果类型: Article
• 署名作者: Qiu, Chengxiang; Martin, Beth K.; Welsh, Ian C.; Daza, Riza M.; Le, Truc-Mai; Huang, Xingfan; Nichols, Eva K.; Taylor, Megan L.; Fulton, Olivia; O'Day, Diana R.; Gomes, Anne Roshella; Ilcisin, Saskia; Srivatsan, Sanjay; Deng, Xinxian; Disteche, Christine M.; Noble, William Stafford; Hamazaki, Nobuhiko; Moens, Cecilia B.; Kimelman, David; Cao, Junyue; Schier, Alexander F.; Spielmann, Malte; Murray, Stephen A.; Trapnell, Cole; Shendure, Jay
• 署名单位: University of Washington; University of Washington Seattle; Jackson Laboratory; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; Rockefeller University; University of Basel; Max Planck Society; University of Lubeck; University of Kiel; Schleswig Holstein University Hospital; University of Kiel; German Centre for Cardiovascular Research
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6634
• DOI: 10.1038/s41586-024-07069-w
• 发表日期: 2024-02-29
• 关键词: regulatory network; specification; morphogenesis; lineage; Heterogeneity; population; expression; organizer; DYNAMICS; nematode

摘要

The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans1,2. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing3 to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation (embryonic day 8) to birth (postnatal day 0). From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis and of kidney, mesenchyme, retina and early neurons. We leverage the temporal resolution and sampling depth of these whole-embryo snapshots, together with published data4-8 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 genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal 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. Single-cell transcriptome profiling of mouse embryos and newborn pups is combined with previously published data to construct a tree of cell-type relationships tracing development from zygote to birth.