Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
Publication year
2017Author(s)
Source
Genome Biology, 18, 1, (2017), pp. 18ISSN
Publication type
Article / Letter to editor
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Organization
Molecular Biology
Human Genetics
Journal title
Genome Biology
Volume
vol. 18
Issue
iss. 1
Page start
p. 18
Subject
Molecular Biology; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical NeuroscienceAbstract
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 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+ naive 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. CONCLUSIONS: 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 .
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- Academic publications [238426]
- Electronic publications [122508]
- Faculty of Medical Sciences [90358]
- Faculty of Science [34985]
- Open Access publications [97504]
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