Natural killer cells (NK-cells), are a type of cytotoxic lymphocyte critical to the innate immune system. NK-cells respond to virus-infected cells, and also to tumor formation, and the ability to recognize stressed cells in the absence of antibodies and MHC allows for a much faster immune reaction as well as destruction of cells that cannot be detected and destroyed by other immune cells. In addition, NK-cells secret cytokines that boost the antitumor immunity and they also display memory cell-like features.

In the Blood Atlas we have 97 cell lineage enriched genes and 16 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 378 genes are cell lineage group enriched and an additional 6 genes are enhanced in this cell lineage. Altogether, 481 genes are elevated and among these 120 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The NK-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. Monocytes, T- and B-cells were eliminated by selecting CD14neg/SSClow and CD3neg/CD19neg sub-population of lymphocytes (FSClow/SSClow). At the final step, population of CD56+/SSClow was selected and 2,300 – 5,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 53% (n=10485) of all human proteins (n=19,670) are expressed in the NK-cells and 183 of these genes show an elevated expression in NK-cells compared to the other 17 cell types (see figure below).

Figure 1. The distribution of all genes across the five specificity categories based on transcript abundance in NK-cells as well as in the other 17 cell types.

Table 1. Number of genes in the subdivided categories of elevated expression in NK-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Cell type enriched 712240 97
Group enriched 0761052 183
Cell type enhanced 4376721 192
Total 1141741813 472

Table 2. The genes with the highest level of enriched expression in NK-cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of NK-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
COX6A2 cytochrome c oxidase subunit 6A2 Detected in single 16.1 125
ZMAT4 zinc finger matrin-type 4 Detected in single 13.7 115
KIR2DL4 killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4 Detected in single 3.2 56
EXOC1L exocyst complex component 1 like Detected in single 2.7 52
MAPK12 mitogen-activated protein kinase 12 Detected in single 1.0 31
TTLL10 tubulin tyrosine ligase like 10 Detected in single 0.8 29
IL37 interleukin 37 Detected in single 0.7 28
GHSR growth hormone secretagogue receptor Detected in single 0.6 25
BAALC BAALC, MAP3K1 and KLF4 binding Detected in single 4.9 25
GPC6 glypican 6 Detected in single 0.5 23
C12orf71 chromosome 12 open reading frame 71 Detected in single 1.8 23
EPS8L3 EPS8 like 3 Detected in single 0.4 22