Identification of the earliest NK-cell precursor in the mouse BM

Natural killer (NK) cells are generated in the bone marrow (BM) from lymphoid progenitors. Although several different maturation states of committed NK cells have been described, the initial stages of NK-cell differentiation from the common lymphoid progenitor are not well understood. Here we describe the identification of the earliest committed NK-cell precursors in the BM. These precursors, termed pre-pro NK cells, lack the expression of most canonical NK cell-specific surface markers but express the transcription factor inhibitor of DNA binding 2 and high levels of the IL-7 receptor. In vitro differentiation studies demonstrate that pre-pro NK cells are committed to NK-cell lineage and appear to be upstream of the previously identified NK-cell progenitor population.