Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide a...
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| Veröffentlicht in: | Genome Biology 2017-01, Vol.18 (1), p.18-18, Article 18 |
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| creator | 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 |
| description | A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.
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.
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 . |
| doi_str_mv | 10.1186/s13059-017-1156-8 |
| format | Article |
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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.
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 .</description><identifier>ISSN: 1474-760X</identifier><identifier>ISSN: 1474-7596</identifier><identifier>EISSN: 1474-760X</identifier><identifier>DOI: 10.1186/s13059-017-1156-8</identifier><identifier>PMID: 28126036</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; analytical methods ; Bioinformatics ; CD14 antigen ; CD16 antigen ; CD4 antigen ; CD45RA antigen ; Chromatin ; Cluster Analysis ; Comparative analysis ; CpG Islands ; Deoxyribonucleic acid ; Differential variability ; DNA ; DNA Methylation ; Enhancers ; environmental exposure ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Fc receptors ; Female ; Functional plasticity ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; genes ; Genetic aspects ; Genetic transcription ; Genetic Variation ; Genome-Wide Association Study ; Genomes ; Genomics ; Heterogeneity ; Humans ; Immune cells ; Immune system ; Immune System - cytology ; Immune System - immunology ; Immune System - metabolism ; Inflammation ; Leukocytes (neutrophilic) ; Lymphocytes ; Lymphocytes T ; Male ; Monocytes ; Neutrophils ; Neutrophils - metabolism ; Organ Specificity - genetics ; Phenotypic plasticity ; Sex Factors ; T cells ; T-lymphocytes ; Transcription ; transcription (genetics) ; Transcription, Genetic</subject><ispartof>Genome Biology, 2017-01, Vol.18 (1), p.18-18, Article 18</ispartof><rights>COPYRIGHT 2017 BioMed Central Ltd.</rights><rights>2017. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>info:eu-repo/semantics/openAccess © Ecker E, et al. 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<a href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</a>), 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. <a href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</a></rights><rights>The Author(s). 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c703t-7aff618d29ac4b4bf3e7358ac74c89ca172926ad6805be1892cda26d1d0038073</citedby><cites>FETCH-LOGICAL-c703t-7aff618d29ac4b4bf3e7358ac74c89ca172926ad6805be1892cda26d1d0038073</cites><orcidid>0000-0002-8230-0116 ; 0000-0001-5648-1710</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270224/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270224/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,26951,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28126036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ecker, Simone</creatorcontrib><creatorcontrib>Chen, Lu</creatorcontrib><creatorcontrib>Pancaldi, Vera</creatorcontrib><creatorcontrib>Bagger, Frederik O</creatorcontrib><creatorcontrib>Fernández, José María</creatorcontrib><creatorcontrib>Carrillo de Santa Pau, Enrique</creatorcontrib><creatorcontrib>Juan, David</creatorcontrib><creatorcontrib>Mann, Alice L</creatorcontrib><creatorcontrib>Watt, Stephen</creatorcontrib><creatorcontrib>Casale, Francesco Paolo</creatorcontrib><creatorcontrib>Sidiropoulos, Nikos</creatorcontrib><creatorcontrib>Rapin, Nicolas</creatorcontrib><creatorcontrib>Merkel, Angelika</creatorcontrib><creatorcontrib>Stunnenberg, Hendrik G</creatorcontrib><creatorcontrib>Stegle, Oliver</creatorcontrib><creatorcontrib>Frontini, Mattia</creatorcontrib><creatorcontrib>Downes, Kate</creatorcontrib><creatorcontrib>Pastinen, Tomi</creatorcontrib><creatorcontrib>Kuijpers, Taco W</creatorcontrib><creatorcontrib>Rico, Daniel</creatorcontrib><creatorcontrib>Valencia, Alfonso</creatorcontrib><creatorcontrib>Beck, Stephan</creatorcontrib><creatorcontrib>Soranzo, Nicole</creatorcontrib><creatorcontrib>Paul, Dirk S</creatorcontrib><creatorcontrib>BLUEPRINT Consortium</creatorcontrib><title>Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types</title><title>Genome Biology</title><addtitle>Genome Biol</addtitle><description>A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.
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.
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 .</description><subject>Analysis</subject><subject>analytical methods</subject><subject>Bioinformatics</subject><subject>CD14 antigen</subject><subject>CD16 antigen</subject><subject>CD4 antigen</subject><subject>CD45RA antigen</subject><subject>Chromatin</subject><subject>Cluster Analysis</subject><subject>Comparative analysis</subject><subject>CpG Islands</subject><subject>Deoxyribonucleic acid</subject><subject>Differential variability</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Enhancers</subject><subject>environmental exposure</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Fc receptors</subject><subject>Female</subject><subject>Functional plasticity</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulatory Networks</subject><subject>genes</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Genetic Variation</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Immune cells</subject><subject>Immune system</subject><subject>Immune System - cytology</subject><subject>Immune System - immunology</subject><subject>Immune System - metabolism</subject><subject>Inflammation</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Monocytes</subject><subject>Neutrophils</subject><subject>Neutrophils - metabolism</subject><subject>Organ Specificity - genetics</subject><subject>Phenotypic plasticity</subject><subject>Sex Factors</subject><subject>T cells</subject><subject>T-lymphocytes</subject><subject>Transcription</subject><subject>transcription (genetics)</subject><subject>Transcription, 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Simone</creator><creator>Chen, Lu</creator><creator>Pancaldi, Vera</creator><creator>Bagger, Frederik O</creator><creator>Fernández, José María</creator><creator>Carrillo de Santa Pau, Enrique</creator><creator>Juan, David</creator><creator>Mann, Alice L</creator><creator>Watt, Stephen</creator><creator>Casale, Francesco Paolo</creator><creator>Sidiropoulos, Nikos</creator><creator>Rapin, Nicolas</creator><creator>Merkel, Angelika</creator><creator>Stunnenberg, Hendrik G</creator><creator>Stegle, Oliver</creator><creator>Frontini, Mattia</creator><creator>Downes, Kate</creator><creator>Pastinen, Tomi</creator><creator>Kuijpers, Taco W</creator><creator>Rico, Daniel</creator><creator>Valencia, Alfonso</creator><creator>Beck, Stephan</creator><creator>Soranzo, Nicole</creator><creator>Paul, Dirk S</creator><general>BioMed Central Ltd</general><general>BioMed 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analysis of differential transcriptional and epigenetic variability across human immune cell types</title><author>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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c703t-7aff618d29ac4b4bf3e7358ac74c89ca172926ad6805be1892cda26d1d0038073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Analysis</topic><topic>analytical methods</topic><topic>Bioinformatics</topic><topic>CD14 antigen</topic><topic>CD16 antigen</topic><topic>CD4 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Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types</atitle><jtitle>Genome Biology</jtitle><addtitle>Genome Biol</addtitle><date>2017-01-26</date><risdate>2017</risdate><volume>18</volume><issue>1</issue><spage>18</spage><epage>18</epage><pages>18-18</pages><artnum>18</artnum><issn>1474-760X</issn><issn>1474-7596</issn><eissn>1474-760X</eissn><abstract>A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.
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.
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 .</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>28126036</pmid><doi>10.1186/s13059-017-1156-8</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-8230-0116</orcidid><orcidid>https://orcid.org/0000-0001-5648-1710</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Genome Biology, 2017-01, Vol.18 (1), p.18-18, Article 18 |
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| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5270224 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Recercat; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings; Springer Nature OA Free Journals |
| subjects | Analysis analytical methods Bioinformatics CD14 antigen CD16 antigen CD4 antigen CD45RA antigen Chromatin Cluster Analysis Comparative analysis CpG Islands Deoxyribonucleic acid Differential variability DNA DNA Methylation Enhancers environmental exposure Epigenesis, Genetic Epigenetic inheritance Epigenetics Fc receptors Female Functional plasticity Gene expression Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks genes Genetic aspects Genetic transcription Genetic Variation Genome-Wide Association Study Genomes Genomics Heterogeneity Humans Immune cells Immune system Immune System - cytology Immune System - immunology Immune System - metabolism Inflammation Leukocytes (neutrophilic) Lymphocytes Lymphocytes T Male Monocytes Neutrophils Neutrophils - metabolism Organ Specificity - genetics Phenotypic plasticity Sex Factors T cells T-lymphocytes Transcription transcription (genetics) Transcription, Genetic |
| title | Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T13%3A57%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-wide%20analysis%20of%20differential%20transcriptional%20and%20epigenetic%20variability%20across%20human%20immune%20cell%20types&rft.jtitle=Genome%20Biology&rft.au=Ecker,%20Simone&rft.aucorp=BLUEPRINT%20Consortium&rft.date=2017-01-26&rft.volume=18&rft.issue=1&rft.spage=18&rft.epage=18&rft.pages=18-18&rft.artnum=18&rft.issn=1474-760X&rft.eissn=1474-760X&rft_id=info:doi/10.1186/s13059-017-1156-8&rft_dat=%3Cgale_pubme%3EA479093690%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2208012402&rft_id=info:pmid/28126036&rft_galeid=A479093690&rfr_iscdi=true |