Cell
Volume 184, Issue 11, 27 May 2021, Pages 2825-2842.e22
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Article
A single-embryo, single-cell time-resolved model for mouse gastrulation

https://doi.org/10.1016/j.cell.2021.04.004Get rights and content
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Highlights

  • Single-embryo scRNA-seq synthesis of morphology and transcriptional staging

  • A network flow model infers differentiation of embryonic cell ensembles

  • Gastrulation is dominated by progenitor states that continuously multi-furcate

  • Single-embryo chimeras control functional studies of TFs over time and lineage

Summary

Mouse embryonic development is a canonical model system for studying mammalian cell fate acquisition. Recently, single-cell atlases comprehensively charted embryonic transcriptional landscapes, yet inference of the coordinated dynamics of cells over such atlases remains challenging. Here, we introduce a temporal model for mouse gastrulation, consisting of data from 153 individually sampled embryos spanning 36 h of molecular diversification. Using algorithms and precise timing, we infer differentiation flows and lineage specification dynamics over the embryonic transcriptional manifold. Rapid transcriptional bifurcations characterize the commitment of early specialized node and blood cells. However, for most lineages, we observe combinatorial multi-furcation dynamics rather than hierarchical transcriptional transitions. In the mesoderm, dozens of transcription factors combinatorially regulate multifurcations, as we exemplify using time-matched chimeric embryos of Foxc1/Foxc2 mutants. Our study rejects the notion of differentiation being governed by a series of binary choices, providing an alternative quantitative model for cell fate acquisition.

Keywords

scRNA-seq
developmental biology
mouse gastrulation
network flow model
trajectory inference
cell fate decisions
tetraploid complementation assay
chimera assay

Cited by (0)

4

Present address: UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA

5

These authors contributed equally

6

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