Hagai, Tzachi, Chen, Xi ORCID: 0000-0003-2648-3146, Miragaia, Ricardo J., Rostom, Raghd, Gomes, Tomas, Kunowska, Natalia, Henriksson, Johan, Park, Jong-Eun, Proserpio, Valentina ORCID: 0000-0003-2071-4206, Donati, Giacomo, Bossini-Castillo, Lara ORCID: 0000-0002-5471-5824, Braga, Felipe A. Vieira, Naamati, Guy ORCID: 0000-0002-0523-4071, Fletcher, James, Stephenson, Emily, Vegh, Peter ORCID: 0000-0002-0133-3240, Trynka, Gosia, Kondova, Ivanela, Dennis, Mike, Haniffa, Muzlifah, Nourmohammad, Armita, Laessig, Michael and Teichmann, Sarah A. (2018). Gene expression variability across cells and species shapes innate immunity. Nature, 563 (7730). S. 197 - 217. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hagai, TzachiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, XiUNSPECIFIEDorcid.org/0000-0003-2648-3146UNSPECIFIED
Miragaia, Ricardo J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rostom, RaghdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomes, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kunowska, NataliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henriksson, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Jong-EunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Proserpio, ValentinaUNSPECIFIEDorcid.org/0000-0003-2071-4206UNSPECIFIED
Donati, GiacomoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bossini-Castillo, LaraUNSPECIFIEDorcid.org/0000-0002-5471-5824UNSPECIFIED
Braga, Felipe A. VieiraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naamati, GuyUNSPECIFIEDorcid.org/0000-0002-0523-4071UNSPECIFIED
Fletcher, JamesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stephenson, EmilyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vegh, PeterUNSPECIFIEDorcid.org/0000-0002-0133-3240UNSPECIFIED
Trynka, GosiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kondova, IvanelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dennis, MikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haniffa, MuzlifahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nourmohammad, ArmitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laessig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teichmann, Sarah A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-165885
DOI: 10.1038/s41586-018-0657-2
Journal or Publication Title: Nature
Volume: 563
Number: 7730
Page Range: S. 197 - 217
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SINGLE CELLS; PROTEIN INTERACTIONS; NATURAL-SELECTION; READ ALIGNMENT; GENOME BROWSER; RNA-SEQ; EVOLUTION; HETEROGENEITY; DIVERGENCE; DATABASEMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16588

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