Diversity of human NK cell developmental pathways defined by single-cell analyses

Abstract

Human natural killer (NK) and innate lymphoid cells (ILCs) include diverse specialized phenotypic and functional subsets that reflect their roles as innate immune effector cells present in tissue and circulation. In recent years, significant advances have been made in better defining their tissue resident phenotypes, developmental pathways, and phenotypic plasticity. Here we offer a brief review of new insights into human NK cell diversity specifically defined by next generation sequencing and single-cell transcriptomic studies and integrate these into our current models of human NK cell developmental trajectories and mature subsets. These studies highlight both a deeper understanding of innate lymphoid cell differentiation and homeostasis and underscore critical questions that remain outstanding in the field.

Figure 1.. scRNA-seq reveals the developmental landscape of NK cells.

Left: a revised model of hematopoiesis with continuous cell states. Right: our current knowledge of NK cell differentiation steps including references for human datasets discussed in the text.