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  Gene expression variability across cells and species shapes innate immunity.

Hagai, T., Chen, X., Miragaia, R. J., Rostom, R., Gomes, T., Kunowska, N., et al. (2018). Gene expression variability across cells and species shapes innate immunity. Nature, 563(7730), 197-202. doi:10.1038/s41586-018-0657-2.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-6962-A Version Permalink: http://hdl.handle.net/21.11116/0000-0003-C5B6-1
Genre: Journal Article

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 Creators:
Hagai, T., Author
Chen, X., Author
Miragaia, R. J., Author
Rostom, R., Author
Gomes, T., Author
Kunowska, N., Author
Henriksson, J., Author
Park, J. E., Author
Proserpio, V., Author
Donati, G., Author
Bossini-Castillo, L., Author
Vieira Braga, F. A., Author
Naamati, G., Author
Fletcher, J., Author
Stephenson, E., Author
Vegh, P., Author
Trynka, G., Author
Kondova, I., Author
Dennis, M., Author
Haniffa, M., Author
Nourmohammad, Armita1, Author              Lässig, M., AuthorTeichmann, S. A., Author more..
Affiliations:
1Max Planck Research Group Statistical physics of evolving systems, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2516692              

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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.

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Language(s): eng - English
 Dates: 2018-10-242018-11-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41586-018-0657-2
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Title: Nature
Source Genre: Journal
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Pages: - Volume / Issue: 563 (7730) Sequence Number: - Start / End Page: 197 - 202 Identifier: -