TY - JOUR
T1 - Multi-omics profiling of mouse gastrulation at single-cell resolution
AU - Argelaguet, Ricard
AU - Clark, Stephen J.
AU - Mohammed, Hisham
AU - Stapel, L. Carine
AU - Krueger, Christel
AU - Kapourani, Chantriolnt Andreas
AU - Imaz-Rosshandler, Ivan
AU - Lohoff, Tim
AU - Xiang, Yunlong
AU - Hanna, Courtney W.
AU - Smallwood, Sebastien
AU - Ibarra-Soria, Ximena
AU - Buettner, Florian
AU - Sanguinetti, Guido
AU - Xie, Wei
AU - Krueger, Felix
AU - Göttgens, Berthold
AU - Rugg-Gunn, Peter J.
AU - Kelsey, Gavin
AU - Dean, Wendy
AU - Nichols, Jennifer
AU - Stegle, Oliver
AU - Marioni, John C.
AU - Reik, Wolf
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/12/19
Y1 - 2019/12/19
N2 - 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.
AB - 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.
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U2 - 10.1038/s41586-019-1825-8
DO - 10.1038/s41586-019-1825-8
M3 - Article
C2 - 31827285
AN - SCOPUS:85076568486
SN - 0028-0836
VL - 576
SP - 487
EP - 491
JO - Nature
JF - Nature
IS - 7787
ER -