Genome-wide Analysis of Differential Transcriptional and Epigenetic Variability Across Human Immune Cell Types

Abstract

AbstractBackgroundA healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.ResultsWe applied 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 discovered substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression were found to be implicated in key immune pathways and to associate with cellular properties and environmental exposure. We also observed increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites were enriched at dynamic chromatin regions and active enhancers.ConclusionsOur data highlight the importance of transcriptional and epigenetic variability for the neutrophils’ key role 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.