Ecker, SimoneMerkel, AngelikaBLUEPRINT ConsortiumPaul, Dirk S.2017-05-262017-05-262017Ecker S, Chen L, Pancaldi V, Bagger FO, Fernández JM, Carrillo de Santa Pau E et al. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology. 2017;18:18. DOI: 10.1186/s13059-017-1156-81474-760Xhttp://hdl.handle.net/10230/32168Background: 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.application/pdfeng© Ecker E, et al. 2017. 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13059-017-1156-8Differential variabilityPhenotypic plasticityHeterogeneityImmune cellsMonocytesNeutrophilsT cellsGene expressionDNA methylationinfo:eu-repo/semantics/openAccess