Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types.
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 .
Ecker, S; Chen, L; Pancaldi, V; Bagger, FO; Fernández, JM; Carrillo de Santa Pau, E; Juan, D; Mann, AL; Watt, S; Casale, FP; Sidiropoulos, N; Rapin, N; Merkel, A; BLUEPRINT Consortium, ; Stunnenberg, HG; Stegle, O; Frontini, M; Downes, K; Pastinen, T; Kuijpers, TW; Rico, D; Valencia, A; Beck, S; Soranzo, N; Paul, DS
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