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

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Ecker, S 
Chen, L 
Pancaldi, V 
Bagger, FO 
Fernández, JM 



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:



DNA methylation, differential variability, gene expression, heterogeneity, immune cells, monocytes, neutrophils, phenotypic plasticity, T cells

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Genome Biology

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BioMed Central
Medical Research Council (G0800270)
Medical Research Council (MR/L003120/1)
European Commission (257082)
Wellcome Trust (091310/Z/10/Z)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
European Commission (282510)
Medical Research Council (G0800270/1)
This work is predominantly funded by the EU-FP7 Project BLUEPRINT (HEALTH-F5-2011-282510). S. Ecker is supported by a “la Caixa” pre-doctoral fellowship. V. Pancaldi is supported by a FEBS Long-Term Fellowship. F.O. Bagger is supported by The Lundbeck Foundation. K. Downes is funded as a HSST trainee by NHS Health Education England. M. Frontini is supported by the British Heart Foundation (BHF) Cambridge Centre of Excellence (RE/13/6/30180). S. Beck acknowledges support from the Wellcome Trust (WT99148), a Royal Society Wolfson Research Merit Award (WM100023), and the UK National Institute for Health Research (NIHR) UCLH Biomedical Research Centre (BRC84/CN/SB/5984). N. Soranzo’s research is supported by the Wellcome Trust (WT098051 and WT091310), EPIGENESYS (257082), and NIHR Cambridge Biomedical Research Centre (BRC). The INB-CNIO Unit is a member of ProteoRed (PRB2-ISCIII) and is supported by PE I + D + i 2013–2016 (PT13/0001), ISCIII, and FEDER. The Cardiovascular Epidemiology Unit is supported by the UK Medical Research Council (G0800270), BHF (SP/09/002), and NIHR Cambridge BRC.