Gene expression variability across cells and species shapes innate immunity

Tzachi Hagai (), Xi Chen, Ricardo J. Miragaia, Raghd Rostom, Tomás Gomes, Natalia Kunowska, Johan Henriksson, Jong-Eun Park, Valentina Proserpio, Giacomo Donati, Lara Bossini-Castillo, Felipe A. Vieira Braga, Guy Naamati, James Fletcher, Emily Stephenson, Peter Vegh, Gosia Trynka, Ivanela Kondova, Mike Dennis, Muzlifah Haniffa, Armita Nourmohammad, Michael Lässig and Sarah A. Teichmann ()
Additional contact information
Tzachi Hagai: Wellcome Sanger Institute
Xi Chen: Wellcome Sanger Institute
Ricardo J. Miragaia: Wellcome Sanger Institute
Raghd Rostom: Wellcome Sanger Institute
Tomás Gomes: Wellcome Sanger Institute
Natalia Kunowska: Wellcome Sanger Institute
Johan Henriksson: Wellcome Sanger Institute
Jong-Eun Park: Wellcome Sanger Institute
Valentina Proserpio: University of Turin
Giacomo Donati: University of Turin
Lara Bossini-Castillo: Wellcome Sanger Institute
Felipe A. Vieira Braga: Wellcome Sanger Institute
Guy Naamati: EMBL- European Bioinformatics Institute
James Fletcher: Institute of Cellular Medicine, Newcastle University
Emily Stephenson: Institute of Cellular Medicine, Newcastle University
Peter Vegh: Institute of Cellular Medicine, Newcastle University
Gosia Trynka: Wellcome Sanger Institute
Ivanela Kondova: Biomedical Primate Research Centre
Mike Dennis: National Infection Service
Muzlifah Haniffa: Institute of Cellular Medicine, Newcastle University
Armita Nourmohammad: Max Planck Institute for Dynamics and Self-Organization
Michael Lässig: University of Cologne
Sarah A. Teichmann: Wellcome Sanger Institute

Nature, 2018, vol. 563, issue 7730, 197-202

Abstract: 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.

Keywords: Transcriptional Variability; Stimulation Time Course; dsRNA Stimulation; Promoter Architecture; Annotated Transcriptome (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0657-2

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