GSE119562
Definition of Natural Killer cell heterogeneity in humans and mice by high-throughput single-cell RNA sequencing
Natural Killer (NK) cells are innate lymphoid cells (ILCs) involved in antimicrobial and antitumoral responses. Several NK cell subsets have been reported in humans and mice, but their heterogeneity across organs and species remains poorly characterized. We assessed the diversity of human and mouse NK cells by single-cell RNA sequencing on thousands of individual cells isolated from spleen and blood. Unbiased transcriptional clustering revealed two distinct signatures differentiating between splenic and blood NK cells. This analysis at single-cell resolution identified three subpopulations in mouse spleen and four in human spleen, and two subsets each in mouse and human blood. A comparison of transcriptomic profiles within and between species highlighted the similarity of the two major subsets, NK1 and NK2, across organs and species. This unbiased approach provides new insight into the biology of NK cells and establishes a rationale for the translation of mouse studies to human physiology and disease. Overall design: Spleen and Blood paired NK cells from 3 individual human brain dead donors (CD45+ CD3– CD14– CD19– CD56+) and 3*5 pooled mice (CD45+ CD3– CD19– NKp46+ NK1.1+) were sorted. Sample 1 : Frozen live spleen NK cells from donor 1 mixed with fresh live spleen NK cells from mouse group 1. Sample 2 : Frozen live spleen NK cells from donor 2 mixed with fresh live spleen NK cells from mouse group 2. Sample 3 : Frozen live spleen NK cells from donor 3 mixed with fresh live spleen NK cells from mouse group 3. Sample 4 : Frozen live blood NK cells from donor 1 mixed with fresh live blood NK cells from mouse group 1. Sample 5 : Frozen live blood NK cells from donor 2 mixed with fresh live blood NK cells from mouse group 2. Sample 6 : Frozen live blood NK cells from donor 3 mixed with fresh live blood NK cells from mouse group 3.