Document Type

Article

Publication Date

3-1-2022

Publication Title

Nature genetics

Keywords

JMG

JAX Source

Nat Genet 2022 Mar; 54(3):328-341

Volume

54

Issue

3

First Page

328

Last Page

341

ISSN

1546-1718

PMID

35288709

DOI

https://doi.org/10.1038/s41588-022-01018-x

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.

Comments

This is an open access article distributed under the terms of the Creative Commons Attribution License.

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