Systematic reconstruction of cellular trajectories across mouse embryogenesis.
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IF: 41.307
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Cited by: 4
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Abstract

Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single-cell zygote gives rise to millions of cells expressing a panoply of molecular programs. Although intensively studied, a comprehensive delineation of the major cellular trajectories that comprise mammalian development in vivo remains elusive. Here, we set out to integrate several single-cell RNA-sequencing (scRNA-seq) datasets that collectively span mouse gastrulation and organogenesis, supplemented with new profiling of ~150,000 nuclei from approximately embryonic day 8.5 (E8.5) embryos staged in one-somite increments. Overall, we define cell states at each of 19 successive stages spanning E3.5 to E13.5 and heuristically connect them to their pseudoancestors and pseudodescendants. Although constructed through automated procedures, the resulting directed acyclic graph (TOME (trajectories of mammalian embryogenesis)) is largely consistent with our contemporary understanding of mammalian development. We leverage TOME to systematically nominate transcription factors (TFs) as candidate regulators of each cell type's specification, as well as 'cell-type homologs' across vertebrate evolution.

Keywords

Seurat
GEO-seq

MeSH terms

Animals
Embryo, Mammalian
Embryonic Development
Gastrulation
Mammals
Mice
Organogenesis

Authors

Qiu, Chengxiang
Cao, Junyue
Martin, Beth K
Li, Tony
Welsh, Ian C
Srivatsan, Sanjay
Huang, Xingfan
Calderon, Diego
Noble, William Stafford
Disteche, Christine M
Murray, Stephen A
Spielmann, Malte
Moens, Cecilia B
Trapnell, Cole
Shendure, Jay

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