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Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immunity

Santiago J. Carmona, View ORCID ProfileSarah A. Teichmann, Lauren Ferreira, Iain C. Macaulay, Michael J.T. Stubbington, Ana Cvejic, David Gfeller
doi: https://doi.org/10.1101/074344
Santiago J. Carmona
1Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland
2Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
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Sarah A. Teichmann
3European Molecular Biology Laboratory European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
4Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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  • ORCID record for Sarah A. Teichmann
  • For correspondence: saraht@ebi.ac.uk as889@cam.ac.uk david.gfeller@unil.ch
Lauren Ferreira
4Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
5Department of Haematology, University of Cambridge, Cambridge, UK
6Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, Cambridge, CB2 1QR, UK
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Iain C. Macaulay
7Sanger Institute–EBI Single-Cell Genomics Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
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Michael J.T. Stubbington
3European Molecular Biology Laboratory European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
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Ana Cvejic
4Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
5Department of Haematology, University of Cambridge, Cambridge, UK
6Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, Cambridge, CB2 1QR, UK
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  • For correspondence: saraht@ebi.ac.uk as889@cam.ac.uk david.gfeller@unil.ch
David Gfeller
1Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland
2Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
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  • For correspondence: saraht@ebi.ac.uk as889@cam.ac.uk david.gfeller@unil.ch
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Abstract

The immune system of vertebrate species consists of many different cell types that have distinct functional roles and are subject to different evolutionary pressures. Here, we first analysed gene conservation of all major immune cell types in human and mouse. Our results revealed higher gene turnover and faster evolution of trans-membrane proteins in NK cells compared to other immune cell populations, and especially T cells, but similar conservation of nuclear and cytoplasmic protein coding genes. To validate these findings in a distant vertebrate species, we used single-cell RNA-Sequencing of lck:GFP cells in zebrafish to obtain the first transcriptome of specific immune cell types in a non-mammalian species. Unsupervised clustering and single-cell TCR locus reconstruction identified three cell populations, T-cells, a novel type of NK-like cells and a smaller population of myeloid-like cells. Differential expression analysis uncovered new immune cell specific genes, including novel immunoglobulin-like receptors, and neofunctionalization of recently duplicated paralogs. Evolutionary analyses confirmed a higher gene turnover and lower conservation of trans-membrane proteins in NK cells compared to T cells in fish species, suggesting that this is a general property of immune cell types across all vertebrates.

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Posted September 12, 2016.
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Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immunity
Santiago J. Carmona, Sarah A. Teichmann, Lauren Ferreira, Iain C. Macaulay, Michael J.T. Stubbington, Ana Cvejic, David Gfeller
bioRxiv 074344; doi: https://doi.org/10.1101/074344
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Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immunity
Santiago J. Carmona, Sarah A. Teichmann, Lauren Ferreira, Iain C. Macaulay, Michael J.T. Stubbington, Ana Cvejic, David Gfeller
bioRxiv 074344; doi: https://doi.org/10.1101/074344

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