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; Valencia, Alfonso; Beck, Stephan; Soranzo, Nicole; Paul, Dirk S

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

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spelling	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell typesEcker, SimoneChen, LuPancaldi, VeraBagger, Frederik OFernández, José MaríaCarrillo-de-Santa-Pau, EnriqueJuan, DavidMann, Alice LWatt, StephenCasale, Francesco PaoloSidiropoulos, NikosRapin, NicolasMerkel, AngelikaStunnenberg, Hendrik GStegle, OliverFrontini, MattiaDownes, KatePastinen, TomiKuijpers, Taco WRico, DanielValencia, AlfonsoBeck, StephanSoranzo, NicolePaul, Dirk SCluster AnalysisCpG IslandsDNA MethylationFemaleGene Expression ProfilingGene Regulatory NetworksGenetic VariationHumansImmune SystemMaleNeutrophilsOrgan SpecificitySex FactorsEpigenesis, GeneticGene Expression RegulationGenome-Wide Association StudyTranscription, GeneticBACKGROUND: 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 .BioMed Central (BMC)Fundación La CaixaUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)National Institute for Health Research (Reino Unido)Medical Research Council (Reino Unido)Unión Europea. Comisión Europea. 7 Programa MarcoWellcome TrustRoyal Society Wolfson Research Merit Award20192019-02-2720172017-01-2620172017-01-26journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/7240reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEC HEALTH-F5-2011-282510 Not availableES PT13 0001open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/72402026-06-12T12:43:37Z
dc.title.none.fl_str_mv	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
title	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
spellingShingle	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types Ecker, Simone 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
title_short	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
title_full	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
title_fullStr	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
title_full_unstemmed	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
title_sort	Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
dc.creator.none.fl_str_mv	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
author	Ecker, Simone
author_facet	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
author_role	author
author2	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
author2_role	author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Fundación La Caixa Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) National Institute for Health Research (Reino Unido) Medical Research Council (Reino Unido) Unión Europea. Comisión Europea. 7 Programa Marco Wellcome Trust Royal Society Wolfson Research Merit Award
dc.subject.none.fl_str_mv	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
topic	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
description	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 .
publishDate	2017
dc.date.none.fl_str_mv	2017 2017-01-26 2017 2017-01-26 2019 2019-02-27
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12105/7240
url	http://hdl.handle.net/20.500.12105/7240
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	EC HEALTH-F5-2011-282510 Not available ES PT13 0001
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	BioMed Central (BMC)
publisher.none.fl_str_mv	BioMed Central (BMC)
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

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