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Single cell multi-omics profiling reveals a hierarchical epigenetic landscape during mammalian germ layer specification: Supplementary Figures [article]

Ricard Argelaguet, Hisham Mohammed, Stephen Clark, Carine Stapel, Christel Krueger, Chantriolnt Andreas Kapourani, Yunlong Xiang, Courtney Hanna, Sebastien Smallwood, Ximena Ibarra Soria, Florian Buettner, Guido Sanguinetti (+9 others)
2019 bioRxiv   pre-print

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Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan. Recent studies employing single cell RNA-sequencing have identified major transcriptional changes associated with germ layer specification. 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 epigenetic layers is unclear. Here we
more » ... cribe the first single cell triple-omics map of chromatin accessibility, DNA methylation and RNA expression during the exit from pluripotency and the onset of gastrulation in mouse embryos. We find dynamic dependencies between the different molecular layers, with evidence for distinct modes of epigenetic regulation. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of local lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements, driven by loss of methylation in enhancer marks and a concomitant increase of chromatin accessibility. In striking contrast, the epigenetic landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or epigenetically remodelled prior to overt cell fate decisions during gastrulation, providing the molecular logic for a hierarchical emergence of the primary germ layers.
doi:10.1101/519207 fatcat:56pcfobfnreibj4ka4bigetbne
Citation

Ricard Argelaguet, Hisham Mohammed, Stephen Clark, Carine Stapel, Christel Krueger, Chantriolnt Andreas Kapourani, Yunlong Xiang, Courtney Hanna, Sebastien Smallwood, Ximena Ibarra Soria, Florian Buettner, Guido Sanguinetti, Felix Krueger, Wei Xie, Peter Rugg-Gunn, Gavin Kelsey, Wendy Dean, Jennifer Nichols, Oliver Stegle, John C Marioni, Wolf Reik. "Single cell multi-omics profiling reveals a hierarchical epigenetic landscape during mammalian germ layer specification: Supplementary Figures." bioRxiv (2019)