TY - JOUR
T1 - Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
AU - Ecker, Simone
AU - Chen, Lu
AU - Pancaldi, Vera
AU - Bagger, Frederik O.
AU - Fernández, José María
AU - Carrillo de Santa Pau, Enrique
AU - Juan, David
AU - Mann, Alice L.
AU - Watt, Stephen
AU - Casale, Francesco Paolo
AU - Sidiropoulos, Nikos
AU - Rapin, Nicolas
AU - Merkel, Angelika
AU - Stunnenberg, Hendrik G.
AU - Stegle, Oliver
AU - Frontini, Mattia
AU - Downes, Kate
AU - Pastinen, Tomi
AU - Kuijpers, Taco W.
AU - Rico, Daniel
AU - Valencia, Alfonso
AU - Beck, Stephan
AU - Soranzo, Nicole
AU - Paul, Dirk S.
AU - AUTHOR GROUP
AU - Albers, Cornelis A.
AU - Amstislavskiy, Vyacheslav
AU - Ashford, Sofie
AU - Bomba, Lorenzo
AU - Bujold, David
AU - Burden, Frances
AU - Busche, Stephan
AU - Caron, Maxime
AU - Chen, Shu-Huang
AU - Cheung, Warren A.
AU - Clarke, Laura
AU - Colgiu, Irina
AU - Datta, Avik
AU - Delaneau, Oliver
AU - Elding, Heather
AU - Farrow, Samantha
AU - Garrido-Martín, Diego
AU - Ge, Bing
AU - Guigo, Roderic
AU - Iotchkova, Valentina
AU - Kundu, Kousik
AU - Kwan, Tony
AU - Lambourne, John J.
AU - Lowy, Ernesto
AU - Mead, Daniel
AU - Pourfarzad, Farzin
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.1186/s13059-017-1156-8
DO - https://doi.org/10.1186/s13059-017-1156-8
M3 - Article
C2 - 28126036
SN - 1465-6906
VL - 18
SP - 18
JO - Genome Biology
JF - Genome Biology
IS - 1
ER -