Forskning ved Københavns Universitet - Københavns Universitet


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

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  • Simone Ecker
  • Lu Chen
  • Vera Pancaldi
  • Frederik O. Bagger
  • José María Fernández
  • Enrique Carrillo de Santa Pau
  • David Juan
  • Alice L. Mann
  • Stephen Watt
  • Francesco Paolo Casale
  • Nicolas Philippe Jean-Pierre Rapin
  • Angelika Merkel
  • Hendrik G Stunnenberg
  • Oliver Stegle
  • Mattia Frontini
  • Kate Downes
  • Tomi Pastinen
  • Taco W Kuijpers
  • Daniel Rico
  • Alfonso Valencia
  • Stephan Beck
  • Nicole Soranzo
  • Dirk S. Paul
  • Cornelis A. Albers
  • Vyacheslav Amstislavskiy
  • Sofie Ashford
  • Lorenzo Bomba
  • David Bujold
  • Frances Burden
  • Stephan Busche
  • Maxime Caron
  • Shu-Huang Chen
  • Warren A. Cheung
  • Laura Clarke
  • Irina Colgiu
  • Avik Datta
  • Oliver Delaneau
  • Heather Elding
  • Samantha Farrow
  • Diego Garrido-Martín
  • Bing Ge
  • Roderic Guigo
  • Valentina Iotchkova
  • Kousik Kundu
  • Tony Kwan
  • John J. Lambourne
  • Ernesto Lowy
  • Daniel Mead
  • Farzin Pourfarzad
  • Adriana Redensek
  • Karola Rehnstrom
  • Augusto Rendon
  • David M. Richardson
  • Thomas Risch
  • Sophia Rowlston
  • Xiaojian Shao
  • Marie Michelle Simon
  • Marc Sultan
  • Klaudia Walter
  • Steven P. Wilder
  • Ying Yan
  • Stylianos E. Antonarakis
  • Guillaume Bourque
  • Emmanouil T. Dermitzakis
  • Paul Flicek
  • Hans Lehrach
  • Joost H A Martens
  • Marie-Laure Yaspo
  • Willem H. Ouwehand

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:

TidsskriftGenome Biology
Udgave nummer1
Antal sider17
StatusUdgivet - 26 jan. 2017

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