Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Simone Ecker, Lu Chen, Vera Pancaldi, Frederik O. Bagger, José María Fernández, Enrique Carrillo de Santa Pau, David Juan, Alice L. Mann, Stephen Watt, Francesco Paolo Casale, Nikos Sidiropoulos, Nicolas Rapin, Angelika Merkel, BLUEPRINT Consortium, Hendrik G. Stunnenberg, Oliver Stegle, Mattia Frontini, Kate Downes, Tomi Pastinen, Taco W. Kuijpers, Daniel Rico, Alfonso Valencia, Stephan Beck, Nicole Soranzo, Dirk S. Paul

ABSTRACT

BACKGROUND: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. RESULTS: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16- monocytes, CD66b+CD16+ neutrophils, and CD4+CD45RA+ naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers. CONCLUSIONS: Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability . More... »

PAGES

18

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-017-1156-8

    DOI

    http://dx.doi.org/10.1186/s13059-017-1156-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1074202887

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28126036


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