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

Lookup NU author(s): Dr Daniel Rico RodriguezORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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

Publication metadata

Author(s): Ecker S, Chen L, Pancaldi V, Bagger FO, Fernandez 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 B, Soranzo N, Paul DS

Publication type: Article

Publication status: Published

Journal: Genome Biology

Year: 2017

Volume: 18

Online publication date: 26/01/2017

Acceptance date: 17/01/2017

Date deposited: 27/02/2017

ISSN (print): 1474-7596

ISSN (electronic): 1474-760X

Publisher: BioMed Central Ltd.


DOI: 10.1186/s13059-017-1156-8

PubMed id: 28126036


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