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 Dean, Jennifer Nichols, Oliver Stegle (), John C. Marioni () and Wolf Reik ()
Additional contact information
Ricard Argelaguet: European Bioinformatics Institute (EMBL-EBI)
Stephen J. Clark: Babraham Institute
Hisham Mohammed: Babraham Institute
L. Carine Stapel: Babraham Institute
Christel Krueger: Babraham Institute
Chantriolnt-Andreas Kapourani: University of Edinburgh
Ivan Imaz-Rosshandler: University of Cambridge
Tim Lohoff: Babraham Institute
Yunlong Xiang: Tsinghua University
Courtney W. Hanna: Babraham Institute
Sebastien Smallwood: Babraham Institute
Ximena Ibarra-Soria: University of Cambridge
Florian Buettner: Institute of Computational Biology
Guido Sanguinetti: University of Edinburgh
Wei Xie: Tsinghua University
Felix Krueger: Babraham Institute
Berthold Göttgens: University of Cambridge
Peter J. Rugg-Gunn: Babraham Institute
Gavin Kelsey: Babraham Institute
Wendy Dean: University of Calgary
Jennifer Nichols: University of Cambridge
Oliver Stegle: European Bioinformatics Institute (EMBL-EBI)
John C. Marioni: European Bioinformatics Institute (EMBL-EBI)
Wolf Reik: Babraham Institute

Nature, 2019, vol. 576, issue 7787, 487-491

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1825-8

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