Lineage reprogramming of c-Kit+CD24+ natural killer cells into myeloid cells

Myeloid progenitor cells have generally been considered the exclusive source of myeloid cells under steady-state conditions. Here, we show that NK cells contributed to a myeloid cell lineage pool in naïve and tumor-bearing mice. By using fate tracing of NKp46+ cells, we found evidence that myeloid cell populations could be derived from NK-committed NKp46+ cells. Notably, among mature CD11b+CD27+ NK cells, c-Kit+CD24+ NK cells were capable of differentiating into a range of myeloid lineages in vitro and reprogrammed into neutrophils and monocytes in vivo. In addition to the potential for lineage conversion, c-Kit+CD24+ NK cells retained NK cell phenotypes and effector functions. Mechanistically, GATA-2 was essential for the conversion of the c-Kit+CD24+ NK cells into myeloid cells. Therefore, we discovered that GATA-2-mediated conversion of c-Kit+CD24+ NK cells contributes to myeloid cell development and identified a novel pathway for myeloid lineage commitment in physiological conditions. Overall design: Examination of mRNA profiles of murine NK cells from the spleen/bone marrow by deep sequencing, using HiSeq 2500