Document Type
Article
Publication Date
2-1-2024
Original Citation
Qiu C,
Martin B,
Welsh I,
Daza R,
Le T,
Huang X,
Nichols E,
Taylor M,
Fulton O,
O'Day D,
Gomes A,
Ilcisin S,
Srivatsan S,
Deng X,
Disteche C,
Noble W,
Hamazaki N,
Moens C,
Kimelman D,
Cao J,
Schier A,
Spielmann M,
Murray SA,
Trapnell C,
Shendure J.
A single-cell time-lapse of mouse prenatal development from gastrula to birth. Nature. 2024;626(8001):1084-93
Keywords
JMG, Animals, Female, Mice, Pregnancy, Animals, Newborn, Cell Differentiation, Embryo, Mammalian, Embryonic Development, Gastrula, Gastrulation, Kidney, Mesoderm, Neurons, Retina, Single-Cell Analysis, Somites, Time Factors, Time-Lapse Imaging, Transcription Factors, Transcription, Genetic, Organ Specificity
JAX Source
Nature. 2024;626(8001):1084-93
ISSN
1476-4687
PMID
38355799
DOI
https://doi.org/10.1038/s41586-024-07069-w
Grant
I.C.W. and S.A.M. were supported by NIH grant UM1OD023222 and the JAX Director’s Innovation Fund.
Abstract
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 data 4–8 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.
Comments
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