Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
Creators
- Ecker, Simone1
- Chen, Lu2
- Pancaldi, Vera1
- Bagger, Frederik O.3
- Fernández, José María1
- Carrillo de Santa Pau, Enrique1
- Juan, David1
- Mann, Alice L.2
- Watt, Stephen2
- Casale, Francesco Paolo4
- Sidiropoulos, Nikos5
- Rapin, Nicolas5
- Merkel, Angelika6
- BLUEPRINT Consortium
- Stunnenberg, Hendrik G.7
- Stegle, Oliver4
- Frontini, Mattia3
- Downes, Kate3
- Pastinen, Tomi8
- Kuijpers, Taco W.9
- Rico, Daniel1
- Valencia, Alfonso1
- Beck, Stephan10
- Soranzo, Nicole2
- Paul, Dirk S.10
- 1. Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain
- 2. Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1HH, UK
- 3. Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, Hinxton, UK
- 4. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
- 5. The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen, Denmark
- 6. 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
- 7. Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, 6525GA, The Netherlands
- 8. Department of Human Genetics, McGill University, 740 Dr. Penfield, Montreal, H3A 0G1, Canada
- 9. Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Plesmanlaan 125, Amsterdam, 1066CX, The Netherlands
- 10. UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK
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.
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13059_2017_1156_MOESM1_ESM.pdf
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