Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7240
Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
Ecker, Simone | Chen, Lu | Pancaldi, Vera | Bagger, Frederik O | Fernández, José María | Carrillo de Santa Pau, Enrique | Juan, David | Mann, Alice L | Watt, Stephen | Casale, Francesco Paolo | Sidiropoulos, Nikos | Rapin, Nicolas | Merkel, Angelika | Stunnenberg, Hendrik G | Stegle, Oliver | Frontini, Mattia | Downes, Kate | Pastinen, Tomi | Kuijpers, Taco W | Rico, Daniel CNIC | Valencia, Alfonso CNIO | Beck, Stephan | Soranzo, Nicole | Paul, Dirk S
Genome Biol. 2017;18(1):18.
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+ 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. 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 .
DNA methylation | Differential variability | Gene expression | Heterogeneity | Immune cells | Monocytes | Neutrophils | Phenotypic plasticity | T cells
Cluster Analysis | CpG Islands | DNA Methylation | Female | Gene Expression Profiling | Gene Regulatory Networks | Genetic Variation | Humans | Immune System | Male | Neutrophils | Organ Specificity | Sex Factors | Epigenesis, Genetic | Gene Expression Regulation | Genome-Wide Association Study | Transcription, Genetic
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