Natural killer (NK) cells are innate lymphoid cells with important roles in antiviral and antitumour immunity. Historically, different subsets of NK cells have been distinguished according to a limited set of surface markers. Two Resource articles in Nature Immunology now use sophisticated single-cell technologies and computational tools to identify, define and interrogate NK cell subsets in healthy individuals and in the tumour microenvironment.

Vivier and colleagues analysed single-cell RNA sequencing (scRNA-seq) and CITE-seq data (which simultaneously measures gene and surface protein expression) from 7 publicly available datasets of NK cells in the blood, lung, tonsils and intraepithelial lymphocytes, as well as 22 tumour types from over 700 donors, with the aim of establishing a standardized terminology. They identified three prominent NK cell subsets in healthy human blood (NK1, NK2 and NK3), which could be further differentiated into six distinct subgroups, and defined their key transcription factors, functions and metabolic traits, as well as transcriptional trajectories. Their data also suggested two distinct ontogenetic origins for NK cells, with divergent transcriptional trajectories.