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

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; Nikos Sidiropoulos; 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

doi:10.1186/s13059-017-1156-8

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

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, Nikos Sidiropoulos, Nicolas Philippe Jean-Pierre Rapin, Angelika Merkel, Hendrik G Stunnenberg, Oliver Stegle, Mattia Frontini, Kate Downes, Tomi Pastinen, Taco W Kuijpers, Daniel RicoAlfonso 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

^*Corresponding author for this work

Computational and RNA Biology

48 Citations (Scopus)

151 Downloads (Pure)

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.

Original language	English
Article number	18
Journal	Genome Biology
Volume	18
Issue number	1
Number of pages	17
ISSN	1474-7596
DOIs	https://doi.org/10.1186/s13059-017-1156-8
Publication status	Published - 26 Jan 2017

Keywords

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

Access to Document

10.1186/s13059-017-1156-8Licence: CC BY

Ecker_2017_Genome-wide_analysisFinal published version, 2.05 MBLicence: CC BY

Cite this

Ecker, S., Chen, L., Pancaldi, V., Bagger, F. O., Fernández, J. M., Carrillo de Santa Pau, E., Juan, D., Mann, A. L., Watt, S., Casale, F. P., Sidiropoulos, N., Rapin, N. P. J.-P., Merkel, A., Stunnenberg, H. G., Stegle, O., Frontini, M., Downes, K., Pastinen, T., Kuijpers, T. W., ... Ouwehand, W. H. (2017). Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology, 18(1), Article 18. https://doi.org/10.1186/s13059-017-1156-8

Ecker, S, Chen, L, Pancaldi, V, Bagger, FO, Fernández, JM, Carrillo de Santa Pau, E, Juan, D, Mann, AL, Watt, S, Casale, FP, Sidiropoulos, N, Rapin, NPJ-P, Merkel, A, Stunnenberg, HG, Stegle, O, Frontini, M, Downes, K, Pastinen, T, Kuijpers, TW, Rico, D, Valencia, A, Beck, S, Soranzo, N, Paul, DS, Albers, CA, Amstislavskiy, V, Ashford, S, Bomba, L, Bujold, D, Burden, F, Busche, S, Caron, M, Chen, S-H, Cheung, WA, Clarke, L, Colgiu, I, Datta, A, Delaneau, O, Elding, H, Farrow, S, Garrido-Martín, D, Ge, B, Guigo, R, Iotchkova, V, Kundu, K, Kwan, T, Lambourne, JJ, Lowy, E, Mead, D, Pourfarzad, F, Redensek, A, Rehnstrom, K, Rendon, A, Richardson, DM, Risch, T, Rowlston, S, Shao, X, Simon, MM, Sultan, M, Walter, K, Wilder, SP, Yan, Y, Antonarakis, SE, Bourque, G, Dermitzakis, ET, Flicek, P, Lehrach, H, Martens, JHA, Yaspo, M-L & Ouwehand, WH 2017, 'Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types', Genome Biology, vol. 18, no. 1, 18. https://doi.org/10.1186/s13059-017-1156-8

@article{e446cf86a29a4e7f8f7a11a749aa9fce,

title = "Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types",

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+na{\"i}ve 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 = "Differential variability, DNA methylation, Gene expression, Heterogeneity, Immune cells, Monocytes, Neutrophils, Phenotypic plasticity, T cells",

author = "Simone Ecker and Lu Chen and Vera Pancaldi and Bagger, {Frederik O.} and Fern{\'a}ndez, {Jos{\'e} Mar{\'i}a} and {Carrillo de Santa Pau}, Enrique and David Juan and Mann, {Alice L.} and Stephen Watt and Casale, {Francesco Paolo} and Nikos Sidiropoulos and Rapin, {Nicolas Philippe Jean-Pierre} and Angelika Merkel and Stunnenberg, {Hendrik G} and Oliver Stegle and Mattia Frontini and Kate Downes and Tomi Pastinen and Kuijpers, {Taco W} and Daniel Rico and Alfonso Valencia and Stephan Beck and Nicole Soranzo and Paul, {Dirk S.} and Albers, {Cornelis A.} and Vyacheslav Amstislavskiy and Sofie Ashford and Lorenzo Bomba and David Bujold and Frances Burden and Stephan Busche and Maxime Caron and Shu-Huang Chen and Cheung, {Warren A.} and Laura Clarke and Irina Colgiu and Avik Datta and Oliver Delaneau and Heather Elding and Samantha Farrow and Diego Garrido-Mart{\'i}n and Bing Ge and Roderic Guigo and Valentina Iotchkova and Kousik Kundu and Tony Kwan and Lambourne, {John J.} and Ernesto Lowy and Daniel Mead and Farzin Pourfarzad and Adriana Redensek and Karola Rehnstrom and Augusto Rendon and Richardson, {David M.} and Thomas Risch and Sophia Rowlston and Xiaojian Shao and Simon, {Marie Michelle} and Marc Sultan and Klaudia Walter and Wilder, {Steven P.} and Ying Yan and Antonarakis, {Stylianos E.} and Guillaume Bourque and Dermitzakis, {Emmanouil T.} and Paul Flicek and Hans Lehrach and Martens, {Joost H A} and Marie-Laure Yaspo and Ouwehand, {Willem H.}",

year = "2017",

month = jan,

day = "26",

doi = "10.1186/s13059-017-1156-8",

language = "English",

volume = "18",

journal = "Genome Biology",

issn = "1474-7596",

publisher = "BioMed Central Ltd.",

number = "1",

}

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 Philippe Jean-Pierre

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 - 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

AU - Redensek, Adriana

AU - Rehnstrom, Karola

AU - Rendon, Augusto

AU - Richardson, David M.

AU - Risch, Thomas

AU - Rowlston, Sophia

AU - Shao, Xiaojian

AU - Simon, Marie Michelle

AU - Sultan, Marc

AU - Walter, Klaudia

AU - Wilder, Steven P.

AU - Yan, Ying

AU - Antonarakis, Stylianos E.

AU - Bourque, Guillaume

AU - Dermitzakis, Emmanouil T.

AU - Flicek, Paul

AU - Lehrach, Hans

AU - Martens, Joost H A

AU - Yaspo, Marie-Laure

AU - Ouwehand, Willem H.

PY - 2017/1/26

Y1 - 2017/1/26

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+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.

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+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.

KW - Differential variability

KW - DNA methylation

KW - Gene expression

KW - Heterogeneity

KW - Immune cells

KW - Monocytes

KW - Neutrophils

KW - Phenotypic plasticity

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=85010952342&partnerID=8YFLogxK

U2 - 10.1186/s13059-017-1156-8

DO - 10.1186/s13059-017-1156-8

M3 - Journal article

C2 - 28126036

AN - SCOPUS:85010952342

SN - 1474-7596

VL - 18

JO - Genome Biology

JF - Genome Biology

IS - 1

M1 - 18

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this