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

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 vari...

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Detalles Bibliográficos
Autores: 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, Valencia, Alfonso, Beck, Stephan, Soranzo, Nicole, Paul, Dirk S
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7240
Acceso en línea:http://hdl.handle.net/20.500.12105/7240
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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 .

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