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

Published

Journal Article

A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.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.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 .

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • January 26, 2017

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 18 -

PubMed ID

  • 28126036

Pubmed Central ID

  • 28126036

Electronic International Standard Serial Number (EISSN)

  • 1474-760X

International Standard Serial Number (ISSN)

  • 1474-7596

Digital Object Identifier (DOI)

  • 10.1186/s13059-017-1156-8

Language

  • eng