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dc.contributor.author | Ecker, Simone | |
dc.contributor.author | Chen, Lu | |
dc.contributor.author | Pancaldi, Vera | |
dc.contributor.author | Bagger, Frederik O | |
dc.contributor.author | Fernández, José María | |
dc.contributor.author | Carrillo de Santa Pau, Enrique | |
dc.contributor.author | Juan, David | |
dc.contributor.author | Mann, Alice L | |
dc.contributor.author | Watt, Stephen | |
dc.contributor.author | Casale, Francesco Paolo | |
dc.contributor.author | Sidiropoulos, Nikos | |
dc.contributor.author | Rapin, Nicolas | |
dc.contributor.author | Merkel, Angelika | |
dc.contributor.author | Stunnenberg, Hendrik G | |
dc.contributor.author | Stegle, Oliver | |
dc.contributor.author | Frontini, Mattia | |
dc.contributor.author | Downes, Kate | |
dc.contributor.author | Pastinen, Tomi | |
dc.contributor.author | Kuijpers, Taco W | |
dc.contributor.author | Rico, Daniel | |
dc.contributor.author | Valencia, Alfonso | |
dc.contributor.author | Beck, Stephan | |
dc.contributor.author | Soranzo, Nicole | |
dc.contributor.author | Paul, Dirk S | |
dc.date.accessioned | 2019-02-27T10:00:32Z | |
dc.date.available | 2019-02-27T10:00:32Z | |
dc.date.issued | 2017-01-26 | |
dc.identifier.citation | Genome Biol. 2017;18(1):18. | es_ES |
dc.identifier.issn | 1474-760X | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7240 | |
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 . | es_ES |
dc.description.sponsorship | We 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.language.iso | eng | es_ES |
dc.publisher | BioMed Central (BMC) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | DNA methylation | es_ES |
dc.subject | Differential variability | es_ES |
dc.subject | Gene expression | es_ES |
dc.subject | Heterogeneity | es_ES |
dc.subject | Immune cells | es_ES |
dc.subject | Monocytes | es_ES |
dc.subject | Neutrophils | es_ES |
dc.subject | Phenotypic plasticity | es_ES |
dc.subject | T cells | es_ES |
dc.subject.mesh | Cluster Analysis | es_ES |
dc.subject.mesh | CpG Islands | es_ES |
dc.subject.mesh | DNA Methylation | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Gene Expression Profiling | es_ES |
dc.subject.mesh | Gene Regulatory Networks | es_ES |
dc.subject.mesh | Genetic Variation | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Immune System | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Neutrophils | es_ES |
dc.subject.mesh | Organ Specificity | es_ES |
dc.subject.mesh | Sex Factors | es_ES |
dc.subject.mesh | Epigenesis, Genetic | es_ES |
dc.subject.mesh | Gene Expression Regulation | es_ES |
dc.subject.mesh | Genome-Wide Association Study | es_ES |
dc.subject.mesh | Transcription, Genetic | es_ES |
dc.title | Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28126036 | es_ES |
dc.format.volume | 18 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 18 | es_ES |
dc.identifier.doi | 10.1186/s13059-017-1156-8 | es_ES |
dc.contributor.funder | Fundación La Caixa | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | National Institute for Health Research (Reino Unido) | |
dc.contributor.funder | Medical Research Council (Reino Unido) | |
dc.contributor.funder | Unión Europea. Comisión Europea. 7 Programa Marco | |
dc.contributor.funder | Wellcome Trust | |
dc.contributor.funder | Royal Society Wolfson Research Merit Award | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1474-760X | es_ES |
dc.relation.publisherversion | https://doi.org/10.1186/s13059-017-1156-8. | es_ES |
dc.identifier.journal | Genome biology | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Biología Computacional Estructural | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/HEALTH-F5-2011-282510 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PT13/0001 | es_ES |
dc.rights.accessRights | open access | es_ES |