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Genome Biol. 2017 Jan 26;18(1):18. doi: 10.1186/s13059-017-1156-8.

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types.

Author information

1
Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain. s.ecker@ucl.ac.uk.
2
UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK. s.ecker@ucl.ac.uk.
3
Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1HH, UK.
4
Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, Hinxton, UK.
5
Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
6
National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
7
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
8
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen, Denmark.
9
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen, Denmark.
10
The Bioinformatics Centre, Department of Biology, Faculty of Natural Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen, Denmark.
11
National Center for Genomic Analysis (CNAG), Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Carrer Baldiri i Reixac 4, 08028, Barcelona, Spain.
12
Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, 6525GA, The Netherlands.
13
British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
14
Department of Human Genetics, McGill University, 740 Dr. Penfield, Montreal, H3A 0G1, Canada.
15
Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Plesmanlaan 125, Amsterdam, 1066CX, The Netherlands.
16
Emma Children's Hospital, Academic Medical Center (AMC), University of Amsterdam, Location H7-230, Meibergdreef 9, Amsterdam, 1105AX, The Netherlands.
17
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
18
UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.
19
Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1HH, UK. ns6@sanger.ac.uk.
20
Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, Hinxton, UK. ns6@sanger.ac.uk.
21
UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK. dsp35@medschl.cam.ac.uk.
22
Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Wort's Causeway, Cambridge, CB1 8RN, UK. dsp35@medschl.cam.ac.uk.

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 .

KEYWORDS:

DNA methylation; Differential variability; Gene expression; Heterogeneity; Immune cells; Monocytes; Neutrophils; Phenotypic plasticity; T cells

PMID:
28126036
PMCID:
PMC5270224
DOI:
10.1186/s13059-017-1156-8
[Indexed for MEDLINE]
Free PMC Article

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