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

Ecker, S; Chen, L; Pancaldi, V; Bagger, FO; Fernández, JM; Carrillo de Santa Pau, E; Juan, D; ... Paul, DS; + view all (2017) Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology , 18 , Article 18. 10.1186/s13059-017-1156-8. Green open access

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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 .

Type: Article
Title: Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13059-017-1156-8
Publisher version: http://dx.doi.org/10.1186/s13059-017-1156-8
Language: English
Additional information: © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: DNA methylation, Differential variability, Gene expression, Heterogeneity, Immune cells, Monocytes, Neutrophils, Phenotypic plasticity, T cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1538559
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