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

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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.

Original languageEnglish
Article number18
JournalGenome Biology
Volume18
Issue number1
DOIs
Publication statusPublished - 26 Jan 2017
Externally publishedYes

Keywords

  • Differential variability
  • DNA methylation
  • Gene expression
  • Heterogeneity
  • Immune cells
  • Monocytes
  • Neutrophils
  • Phenotypic plasticity
  • T cells

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