Gene expression variability across cells and species shapes innate immunity
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/56906 |
Resumo: | As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response. |
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Gene expression variability across cells and species shapes innate immunityScience & TechnologyAs the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.We thank N. Eling, M. Fumagalli, Y. Gilad, O. Laufman, A. Marcovitz, J. Marioni, K. Meyer, M. Muffato, D. Odom, O. Stegle, A. Stern, M. Stubbington, V. Svensson and M. Ward for discussions; G. Emerton, A. Jinat, L. Mamanova, K. Polanski, A. Fullgrabe, N. George, S. Barnett, R. Boyd, S. Patel and C. Gomez for technical assistance; the Hipsci consortium for human fibroblast lines; and members of the Teichmann laboratory for support at various stages. This project was supported by ERC grants (ThDEFINE, ThSWITCH) and an EU FET-OPEN grant (MRG-GRAMMAR No 664918) and Wellcome Sanger core funding (Grant No WT206194). T.H. was supported by an HFSP Long-Term Fellowship and by EMBO Long-Term and Advanced fellowships. V.P. is funded by Fondazione Umberto Veronesi.info:eu-repo/semantics/publishedVersionSpringer NatureUniversidade do MinhoHagai, TzachiChen, XiMiragaia, Ricardo J.Rostom, RaghdGomes, TomásKunowska, NataliaHenriksson, JohanPark, Jong-EunProserpio, ValentinaDonati, GiacomoBossini-Castillo, LaraVieira Braga, Felipe A.Naamati, GuyFletcher, JamesStephenson, EmilyVegh, PeterTrynka, GosiaKondova, IvanelaDennis, MikeHaniffa, MuzlifahNourmohammad, ArmitaLässig, MichaelTeichmann,Sarah A.20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/56906engHagai, Tzachi; Chen, Xi; Miragaia, Ricardo J.; Rostom, Raghd; Gomes, Tomás; Kunowska, Natalia; Henriksson, Johan; Park, Jong-Eun; Proserpio, Valentina; Donati, Giacomo; Bossini-Castillo, Lara; Vieira Braga, Felipe A.; Naamati, Guy; Fletcher, James; Stephenson, Emily; Vegh, Peter; Trynka, Gosia; Kondova, Ivanela; Dennis, Mike; Haniffa, Muzlifah; Nourmohammad, Armita; Lässig, Michael; Teichmann,Sarah A., Gene expression variability across cells and species shapes innate immunity. Nature, 563, 197-202, 20180028-08361476-468710.1038/s41586-018-0657-230356220info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:29:22Zoai:repositorium.sdum.uminho.pt:1822/56906Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:24:21.061786Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Gene expression variability across cells and species shapes innate immunity |
title |
Gene expression variability across cells and species shapes innate immunity |
spellingShingle |
Gene expression variability across cells and species shapes innate immunity Hagai, Tzachi Science & Technology |
title_short |
Gene expression variability across cells and species shapes innate immunity |
title_full |
Gene expression variability across cells and species shapes innate immunity |
title_fullStr |
Gene expression variability across cells and species shapes innate immunity |
title_full_unstemmed |
Gene expression variability across cells and species shapes innate immunity |
title_sort |
Gene expression variability across cells and species shapes innate immunity |
author |
Hagai, Tzachi |
author_facet |
Hagai, Tzachi Chen, Xi Miragaia, Ricardo J. Rostom, Raghd Gomes, Tomás Kunowska, Natalia Henriksson, Johan Park, Jong-Eun Proserpio, Valentina Donati, Giacomo Bossini-Castillo, Lara Vieira Braga, Felipe A. Naamati, Guy Fletcher, James Stephenson, Emily Vegh, Peter Trynka, Gosia Kondova, Ivanela Dennis, Mike Haniffa, Muzlifah Nourmohammad, Armita Lässig, Michael Teichmann,Sarah A. |
author_role |
author |
author2 |
Chen, Xi Miragaia, Ricardo J. Rostom, Raghd Gomes, Tomás Kunowska, Natalia Henriksson, Johan Park, Jong-Eun Proserpio, Valentina Donati, Giacomo Bossini-Castillo, Lara Vieira Braga, Felipe A. Naamati, Guy Fletcher, James Stephenson, Emily Vegh, Peter Trynka, Gosia Kondova, Ivanela Dennis, Mike Haniffa, Muzlifah Nourmohammad, Armita Lässig, Michael Teichmann,Sarah A. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Hagai, Tzachi Chen, Xi Miragaia, Ricardo J. Rostom, Raghd Gomes, Tomás Kunowska, Natalia Henriksson, Johan Park, Jong-Eun Proserpio, Valentina Donati, Giacomo Bossini-Castillo, Lara Vieira Braga, Felipe A. Naamati, Guy Fletcher, James Stephenson, Emily Vegh, Peter Trynka, Gosia Kondova, Ivanela Dennis, Mike Haniffa, Muzlifah Nourmohammad, Armita Lässig, Michael Teichmann,Sarah A. |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/56906 |
url |
http://hdl.handle.net/1822/56906 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hagai, Tzachi; Chen, Xi; Miragaia, Ricardo J.; Rostom, Raghd; Gomes, Tomás; Kunowska, Natalia; Henriksson, Johan; Park, Jong-Eun; Proserpio, Valentina; Donati, Giacomo; Bossini-Castillo, Lara; Vieira Braga, Felipe A.; Naamati, Guy; Fletcher, James; Stephenson, Emily; Vegh, Peter; Trynka, Gosia; Kondova, Ivanela; Dennis, Mike; Haniffa, Muzlifah; Nourmohammad, Armita; Lässig, Michael; Teichmann,Sarah A., Gene expression variability across cells and species shapes innate immunity. Nature, 563, 197-202, 2018 0028-0836 1476-4687 10.1038/s41586-018-0657-2 30356220 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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