CCAAT enhancer binding protein α is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors

The transcription factor CCAAT/enhancer binding protein or (C/EBP alpha) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBP alpha in human granulopoiesis,,ve studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBP alpha initiates with the commitment of multipotential precursors to the myeloid lineage, is specifically upregulated during granulocytic differentiation, and is rapidly downregulated during the alternative monocytic pathway. Conditional expression of C/EBP alpha alone in stably transfected bipotential cells triggers neutrophilic differentiation, concomitant with upregulation of the granulocyte-specific granulocyte colony-stimulating factor receptor and secondary granule protein genes. Moreover, induced expression of C/EBP alpha in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBP alpha serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes.