Ecker, SimoneChen, LuPancaldi, VeraBagger, Frederik OFernández, José MaríaCarrillo-de-Santa-Pau, EnriqueJuan, DavidMann, Alice LWatt, StephenCasale, Francesco PaoloSidiropoulos, NikosRapin, NicolasMerkel, AngelikaStunnenberg, Hendrik GStegle, OliverFrontini, MattiaDownes, KatePastinen, TomiKuijpers, Taco WRico, DanielValencia, AlfonsoBeck, StephanSoranzo, NicolePaul, Dirk S2019-02-272019-02-272017-01-26Genome Biol. 2017;18(1):18.1474-760Xhttp://hdl.handle.net/20.500.12105/7240BACKGROUND: 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 .engVoRhttp://creativecommons.org/licenses/by/4.0/DNA methylationDifferential variabilityGene expressionHeterogeneityImmune cellsMonocytesNeutrophilsPhenotypic plasticityT cellsCluster AnalysisCpG IslandsDNA MethylationFemaleGene Expression ProfilingGene Regulatory NetworksGenetic VariationHumansImmune SystemMaleNeutrophilsOrgan SpecificitySex FactorsEpigenesis, GeneticGene Expression RegulationGenome-Wide Association StudyTranscription, GeneticAtribución 4.0 Internacional281260361811810.1186/s13059-017-1156-81474-760XGenome biologyopen access