CCAAT/Enhancer Binding Protein a Is a Regulatory Switch Sufficient for Induction of Granulocytic Development from Bipotential Myeloid Progenitors

Autor: Radomska, Hanna S., Huettner, Claudia S., Zhang, Pu, Cheng, Tao, Scadden, David T., Tenen, Daniel G.
Zdroj: Molecular and Cellular Biology; July 1998, Vol. 18 Issue: 7 p4301-4314, 14p
Abstrakt: ABSTRACTThe transcription factor CCAAT/enhancer binding protein a (C/EBPa) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBPa in human granulopoiesis, we studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBPa 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/EBPa 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/EBPa in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBPa serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes.
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