Neutrophil production in the BM. The recognized stages of stem cell differentiation that contribute to neutropoiesis are indicated by the names of the neutrophil progenitors in color. Bifurcations into nonneutrophil-producing lineages are indicated in gray. Importantly, the differentiation occurs in a gradual manner (priming) rather than as discrete steps associated with division. The dominant lineage-determining transcription factors are indicated in blue. The first bias toward neutropoiesis starts with a slow and gradual commitment of MPP3s toward the myeloid lineage. MPP3s can proliferate or differentiate into GMPs, which can proliferate and/or physically cluster together into loose patchecs (p) of GMP.89 This clustering facilitates differentiation into compact clusters of (c)GMP that, in turn, differentiate into promyelocytes and myelocytes, thereby forming clusters of these cells in the BM.89 During these last differentiation steps, the progenitors lose their propensity to proliferate (mediated by the expression of C/EBPɛ)2 and continue to mature toward mature neutrophils via metamyelocytes and banded cells (see Figure 2). CDP, common dendritic cell progenitor; cMoP, common monocyte progenitor; EGR1/2, early growth response ½; GATA1/2, GATA binding receptor ½; IRF8, interferon regulatory factor-8; MDP, monocyte/macrophage/DC; NAB-2, NGFI-A binding protein 2; preMono, preMonocyte; SCL, stem cell leukemia.