University of Lausanne researchers identify a novel natural killer-like cell type with single-cell RNA-Seq

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, University of Lausanne and Sanger Institute researchers first analysed conservation of genes specific for all major immune cell types in human and mouse. Their 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, the researchers 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.

Conservation analysis of human and mouse genes differentially expressed
in major immune cell types

A,B: Proportion of human genes specific for distinct immune cell types (T, B, NK and myeloid cells) with orthologs in other species. (A) shows the results for genes coding for transmembrane and secreted proteins and (B) for cytoplasmic and nuclear proteins. C,D: Same analysis as in (A) and (B) using mouse immune cell types’ specific genes.