Understanding natural killer cell biology from a single cell perspective.

During the last decade, advances in single cell technologies have ignited increased understanding of natural killer cells (NK cells), which turned out to be far more complex than originally thought. Ample studies have established tissue-specific phenotypic variation within this cell population; however, the functional implication of this vast variation is still unclear. At single-cell level, the function of a NK cell is tightly regulated by several checkpoints however upon proper recognition the cell can deliver a lytic hit as early as 10 min or could take hours before they can kill their target cells. Moreover, only a fraction of NK cells appears to kill target cells while the larger portion of NK cells appear to be non-cytotoxic. All these studies showed that the NK cell compartment is composed of cells with different functional strengths and efficacies, thereby highlighting the necessity of analytical platforms that allow the study of these important innate immune cells at single-cell level. In this review, we discuss and provide an overview on phenotypical and functional heterogeneity within the NK cell population and subsequently provide information regarding emerging technologies that highlight the importance of single-cell studies to understand the biology of these cells.