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A single-embryo, single-cell time-resolved model for mouse gastrulation

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Item Type:Article
Title:A single-embryo, single-cell time-resolved model for mouse gastrulation
Creators Name:Mittnenzweig, M., Mayshar, Y., Cheng, S., Ben-Yair, R., Hadas, R., Rais, Y., Chomsky, E., Reines, N., Uzonyi, A., Lumerman, L., Lifshitz, A., Mukamel, Z., Orenbuch, A.H., Tanay, A. and Stelzer, Y.
Abstract: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, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press
Volume:184
Number:11
Page Range:2825-2842
Date:27 May 2021
Official Publication:https://doi.org/10.1016/j.cell.2021.04.004
PubMed:View item in PubMed

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