PT  - JOURNAL ARTICLE
AU  - Simone Ecker
AU  - Lu Chen
AU  - Vera Pancaldi
AU  - Frederik O. Bagger
AU  - José Maria Fernandez
AU  - Enrique Carrillo de Santa Pau
AU  - David Juan
AU  - Alice L. Mann
AU  - Stephen Watt
AU  - Francesco Paolo Casale
AU  - Nikos Sidiropoulos
AU  - Nicolas Rapin
AU  - Angelika Merkel
AU  - BLUEPRINT Consortium
AU  - Henk Stunnenberg
AU  - Oliver Stegle
AU  - Mattia Frontini
AU  - Kate Downes
AU  - Tomi Pastinen
AU  - Taco W. Kuijpers
AU  - Daniel Rico
AU  - Alfonso Valencia
AU  - Stephan Beck
AU  - Nicole Soranzo
AU  - Dirk S. Paul
TI  - Genome-wide Analysis of Differential Transcriptional and Epigenetic Variability Across Human Immune Cell Types
AID  - 10.1101/083246
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 083246
4099  - http://biorxiv.org/content/early/2016/10/26/083246.short
4100  - http://biorxiv.org/content/early/2016/10/26/083246.full
AB  - 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 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.Conclusions Our 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.