期刊
GENOME BIOLOGY
卷 18, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13059-017-1156-8
关键词
Differential variability; Phenotypic plasticity; Heterogeneity; Immune cells; Monocytes; Neutrophils; T cells; Gene expression; DNA methylation
资金
- EU-FP7 Project BLUEPRINT [HEALTH-F5-2011-282510]
- la Caixa pre-doctoral fellowship
- FEBS Long-Term Fellowship
- Lundbeck Foundation
- NHS Health Education England
- British Heart Foundation (BHF) Cambridge Centre of Excellence [RE/13/6/30180]
- Wellcome Trust [WT99148, WT098051, WT091310]
- Royal Society Wolfson Research Merit Award [WM100023]
- UK National Institute for Health Research (NIHR) UCLH Biomedical Research Centre [BRC84/CN/SB/5984]
- EPIGENESYS [257082]
- NIHR Cambridge Biomedical Research Centre (BRC)
- ISCIII
- FEDER
- UK Medical Research Council [G0800270]
- BHF [SP/09/002]
- NIHR Cambridge BRC
- PE I + D + i [PT13/0001]
- MRC [G0800270, MR/L003120/1] Funding Source: UKRI
- British Heart Foundation [RG/08/014/24067, RG/13/13/30194] Funding Source: researchfish
- Lundbeck Foundation [R182-2014-3881, R193-2015-1611] Funding Source: researchfish
- Medical Research Council [G0800270, MR/L003120/1, 1365667] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10165, NF-SI-0513-10151] Funding Source: researchfish
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(+) naive 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.
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