Multi-omics profiling of mouse gastrulation at single-cell resolution

Ricard Argelaguet, Stephen J. Clark, Hisham Mohammed, L. Carine Stapel, Christel Krueger, Chantriolnt Andreas Kapourani, Ivan Imaz-Rosshandler, Tim Lohoff, Yunlong Xiang, Courtney W. Hanna, Sebastien Smallwood, Ximena Ibarra-Soria, Florian Buettner, Guido Sanguinetti, Wei Xie, Felix Krueger, Berthold Göttgens, Peter J. Rugg-Gunn, Gavin Kelsey, Wendy DeanJennifer Nichols, Oliver Stegle, John C. Marioni, Wolf Reik

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes1–5. Global epigenetic reprogramming accompanies these changes6–8, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalNature
Volume576
Issue number7787
DOIs
StatePublished - Dec 19 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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