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dc.contributor.authorEcker, Simone
dc.contributor.authorChen, Lu
dc.contributor.authorPancaldi, Vera
dc.contributor.authorBagger, Frederik O
dc.contributor.authorFernández, José María
dc.contributor.authorCarrillo de Santa Pau, Enrique
dc.contributor.authorJuan, David
dc.contributor.authorMann, Alice L
dc.contributor.authorWatt, Stephen
dc.contributor.authorCasale, Francesco Paolo
dc.contributor.authorSidiropoulos, Nikos
dc.contributor.authorRapin, Nicolas
dc.contributor.authorMerkel, Angelika
dc.contributor.authorStunnenberg, Hendrik G
dc.contributor.authorStegle, Oliver
dc.contributor.authorFrontini, Mattia
dc.contributor.authorDownes, Kate
dc.contributor.authorPastinen, Tomi
dc.contributor.authorKuijpers, Taco W
dc.contributor.authorRico, Daniel 
dc.contributor.authorValencia, Alfonso 
dc.contributor.authorBeck, Stephan
dc.contributor.authorSoranzo, Nicole
dc.contributor.authorPaul, Dirk S
dc.identifier.citationGenome Biol. 2017;18(1):18.es_ES
dc.description.abstractBACKGROUND: 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: .es_ES
dc.description.sponsorshipWe would like to thank K. Pearce and M. Kristiansen (UCL Genomics) for processing the Illumina Infinium HumanMethylation450 BeadChips; D. Balzereit, S. Dökel, A. Kovacsovics, and M. Linser (Max Planck Institute for Molecular Genetics) for help with generating the RNA-seq data; B. Phipson (Murdoch Childrens Research Institute), H.C. Bravo (University of Maryland), and P. Guilhamon (UCL Cancer Institute) for advice on statistical analyses; C. Bock (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences) for useful discussions; A. Orozco (University of Costa Rica) for technical support; V. Naranbhai, B. Fairfax, and J. Knight (University of Oxford) for providing access to the neutrophil gene expression data set for replication; and L. Phipps for proofreading the manuscript. We gratefully acknowledge the participation of all NIHR Cambridge BioResource volunteers, and thank the Cambridge BioResource staff for their help with volunteer recruitment. We thank members of the Cambridge BioResource SAB and Management Committee for their support of our study and the NIHR Cambridge Biomedical Research Centre (BRC) for funding. BLUEPRINT Consortium: Cornelis A. Albers (Radboud University), Vyacheslav Amstislavskiy (Max Planck Institute for Molecular Genetics), Sofie Ashford (University of Cambridge), Lorenzo Bomba (Wellcome Trust Sanger Institute), David Bujold (McGill University), Frances Burden (University of Cambridge), Stephan Busche (McGill University), Maxime Caron (McGill University), Shu-Huang Chen (McGill University), Warren A. Cheung (McGill University), Laura Clarke (European Bioinformatics Institute), Irina Colgiu (Wellcome Trust Sanger Institute), Avik Datta (European Bioinformatics Institute), Oliver Delaneau (University of Geneva), Heather Elding (Wellcome Trust Sanger Institute), Samantha Farrow (University of Cambridge), Diego Garrido-Martín (Centre for Genomic Regulation), Bing Ge (McGill University), Roderic Guigo (Centre for Genomic Regulation), Valentina Iotchkova (European Bioinformatics Institute), Kousik Kundu (Wellcome Trust Sanger Institute), Tony Kwan (McGill University), John J. Lambourne (University of Cambridge), Ernesto Lowy (European Bioinformatics Institute), Daniel Mead (Wellcome Trust Sanger Institute), Farzin Pourfarzad (Sanquin Research and Landsteiner Laboratory), Adriana Redensek (McGill University), Karola Rehnstrom (University of Cambridge), Augusto Rendon (University of Cambridge), David Richardson (European Bioinformatics Institute), Thomas Risch (Max Planck Institute for Molecular Genetics), Sophia Rowlston (University of Cambridge), Xiaojian Shao (McGill University), Marie-Michelle Simon (McGill University), Marc Sultan (Max Planck Institute for Molecular Genetics), Klaudia Walter (Wellcome Trust Sanger Institute), Steven P. Wilder (European Bioinformatics Institute), Ying Yan (Wellcome Trust Sanger Institute), Stylianos E. Antonarakis (University of Geneva), Guillaume Bourque (McGill University), Emmanouil T. Dermitzakis (University of Geneva), Paul Flicek (European Bioinformatics Institute), Hans Lehrach (Max Planck Institute for Molecular Genetics), Joost H. A. Martens (Radboud University), Marie-Laure Yaspo (Max Planck Institute for Molecular Genetics), Willem H. Ouwehand (University of Cambridge).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectDNA methylationes_ES
dc.subjectDifferential variabilityes_ES
dc.subjectGene expressiones_ES
dc.subjectImmune cellses_ES
dc.subjectPhenotypic plasticityes_ES
dc.subjectT cellses_ES
dc.subject.meshCluster Analysis es_ES
dc.subject.meshCpG Islands es_ES
dc.subject.meshDNA Methylation es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGene Expression Profiling es_ES
dc.subject.meshGene Regulatory Networks es_ES
dc.subject.meshGenetic Variation es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmune System es_ES
dc.subject.meshMale es_ES
dc.subject.meshNeutrophils es_ES
dc.subject.meshOrgan Specificity es_ES
dc.subject.meshSex Factors es_ES
dc.subject.meshEpigenesis, Genetices_ES
dc.subject.meshGene Expression Regulation es_ES
dc.subject.meshGenome-Wide Association Study es_ES
dc.subject.meshTranscription, Genetices_ES
dc.titleGenome-wide analysis of differential transcriptional and epigenetic variability across human immune cell typeses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderFundacion La Caixaes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderMedical Research Council (United Kingdom)es_ES
dc.contributor.funder7º Programa Marco - Comisión Europeaes_ES
dc.contributor.funderWellcome Trustes_ES
dc.contributor.funderRoyal Society Wolfson Research Merit Awardes_ES
dc.identifier.journalGenome biologyes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Biología Computacional Estructurales_ES

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Atribución 4.0 Internacional
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