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Argelaguet, R.* ; Clark, S.J.* ; Mohammed, H.* ; Stapel, L.C.* ; Krueger, C.* ; Kapourani, C.A.* ; Imaz-Rosshandler, I.* ; Lohoff, T.* ; Xiang, Y.* ; Hanna, C.W.* ; Smallwood, S.* ; Ibarra-Soria, X.* ; Buettner, F. ; Sanguinetti, G.* ; Xie, W.* ; Krueger, F.* ; Göttgens, B.* ; Rugg-Gunn, P.J.* ; Kelsey, G.* ; Dean, W.* ; Nichols, J.* ; Stegle, O.* ; Marioni, J.C.* ; Reik, W.*

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

Nature 576, 487-491 (2019)
Postprint DOI PMC
Open Access Green
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 changes(1-5). Global epigenetic reprogramming accompanies these changes(6-8), 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dna Demethylation; Rna-seq; Methylation; Genome; Tet; Specification; Transcriptome; Enhancers; Gene; Dynamics
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 576, Issue: 7787, Pages: 487-491 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)