Multi-omics profiling of mouse gastrulation at single-cell resolution.
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Authors
Mohammed, Hisham
Krueger, Christel
Xiang, Yunlong
Smallwood, Sebastien
Ibarra-Soria, Ximena
Buettner, Florian
Sanguinetti, Guido
Xie, Wei
Krueger, Felix
Rugg-Gunn, Peter J
Kelsey, Gavin
Dean, Wendy
Marioni, John C
Publication Date
2019-12-11Journal Title
Nature
ISSN
0028-0836
Publisher
Springer Nature
Volume
576
Issue
7787
Pages
487-491
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Argelaguet, R., Clark, S. J., Mohammed, H., Stapel, L. C., Krueger, C., Kapourani, C., Imaz-Rosshandler, I., et al. (2019). Multi-omics profiling of mouse gastrulation at single-cell resolution.. Nature, 576 (7787), 487-491. https://doi.org/10.1038/s41586-019-1825-8
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 changes. Global epigenetic reprogramming accompanies these changes, 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 the first single cell triple-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 TET-mediated demethylation, and a concomitant increase of accessibility. In striking 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 prior to cell fate decisions, providing the molecular logic for a hierarchical emergence of the primary germ layers.
Keywords
Chromatin, Pluripotent Stem Cells, Gastrula, Endoderm, Mesoderm, Animals, Mice, RNA, Factor Analysis, Statistical, Cell Differentiation, Erythropoiesis, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Zinc Fingers, Cell Lineage, Time Factors, Gastrulation, Enhancer Elements, Genetic, Embryoid Bodies, Single-Cell Analysis, Demethylation, Epigenome
Sponsorship
CRUK, Wellcome Trust, MRC, BBSRC, EMBL, EU
Funder references
WELLCOME TRUST (105031/D/14/Z)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (108438/E/15/Z)
MRC (MC_PC_12009)
BBSRC (BB/M004023/1)
BBSRC (BB/S001816/1)
Identifiers
External DOI: https://doi.org/10.1038/s41586-019-1825-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/298216
Rights
All rights reserved