Model for the role of C/EBPα in myeloid lineage commitment. C/EBPα directs CMP to the GMP stage, perhaps via induction of PU.1.^8,9,15  We propose that C/EBPα then interacts with cytokine/TNF-α–activated AP-1 or NF-κB p50 to direct monocytic commitment via further elevation of PU.1. In the presence of alternative signals, C/EBPα contributes to granulopoiesis, but PU.1 level or activity is not further induced. Our findings leave open the possibility that increased C/EBPα in CMPs or HSCs also directly induces monocytic or granulocytic commitment dependent on their expression of requisite cooperating factors.