RT Journal Article
SR Electronic
T1 Genome-wide Analysis of Differential Transcriptional and Epigenetic Variability Across Human Immune Cell Types
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 083246
DO 10.1101/083246
A1 Simone Ecker
A1 Lu Chen
A1 Vera Pancaldi
A1 Frederik O. Bagger
A1 José Maria Fernandez
A1 Enrique Carrillo de Santa Pau
A1 David Juan
A1 Alice L. Mann
A1 Stephen Watt
A1 Francesco Paolo Casale
A1 Nikos Sidiropoulos
A1 Nicolas Rapin
A1 Angelika Merkel
A1 BLUEPRINT Consortium
A1 Henk Stunnenberg
A1 Oliver Stegle
A1 Mattia Frontini
A1 Kate Downes
A1 Tomi Pastinen
A1 Taco W. Kuijpers
A1 Daniel Rico
A1 Alfonso Valencia
A1 Stephan Beck
A1 Nicole Soranzo
A1 Dirk S. Paul
YR 2016
UL http://biorxiv.org/content/early/2016/10/26/083246.abstract
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.