Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types
Santiago J. Carmona1,2, S. A. Teichmann3,4, L. Ferreira4,5,6, I. C. Macaulay7, M. J.T. Stubbington3, A. Cvejic4,5,6 and D. Gfeller1,2
1Ludwig Center for Cancer Research, University of Lausanne, Switzerland; 2Swiss Institute of Bioinformatics (SIB), Switzerland; 3European Molecular Biology Laboratory European Bioinformatics Institute, UK; 4Wellcome Trust Sanger Institute, UK; 5Department of Haematology, University of Cambridge, UK; 6Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, UK; 7Sanger Institute–EBI Single-Cell Genomics Centre, UK
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 conservation of genes specific for 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 types, 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 and obtained 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 the higher gene turnover 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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