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

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• dc.contributor.author Ecker, Simoneca
• dc.contributor.author Merkel, Angelikaca
• dc.contributor.author BLUEPRINT Consortiumca
• dc.contributor.author Paul, Dirk S.ca
• dc.date.accessioned 2017-05-26T07:52:38Z
• dc.date.available 2017-05-26T07:52:38Z
• dc.date.issued 2017
• dc.description.abstract 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.
• dc.description.sponsorship This work is predominantly funded by the EU-FP7 Project BLUEPRINT (HEALTH-F5-2011-282510).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Ecker S, Chen L, Pancaldi V, Bagger FO, Fernández JM, Carrillo de Santa Pau E et al. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology. 2017;18:18. DOI: 10.1186/s13059-017-1156-8
• dc.identifier.doi http://dx.doi.org/10.1186/s13059-017-1156-8
• dc.identifier.issn 1474-760X
• dc.identifier.uri http://hdl.handle.net/10230/32168
• dc.language.iso eng
• dc.publisher BioMed Centralca
• dc.relation.ispartof Genome Biology. 2017;18:18
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
• dc.rights © Ecker E, et al. 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Differential variability
• dc.subject.keyword Phenotypic plasticity
• dc.subject.keyword Heterogeneity
• dc.subject.keyword Immune cells
• dc.subject.keyword Monocytes
• dc.subject.keyword Neutrophils
• dc.subject.keyword T cells
• dc.subject.keyword Gene expression
• dc.subject.keyword DNA methylation
• dc.title Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell typesca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion