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

HS Radomska, CS Huettner, PU Zhang… - … and cellular biology, 1998 - Taylor & Francis
HS Radomska, CS Huettner, PU Zhang, TAO Cheng, DT Scadden, DG Tenen
Molecular and cellular biology, 1998Taylor & Francis
The transcription factor CCAAT/enhancer binding protein α (C/EBPα) regulates a number of
myeloid cell-specific genes. To delineate the role of C/EBPα 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/EBPα initiates with the
commitment of multipotential precursors to the myeloid lineage, is specifically upregulated
during granulocytic differentiation, and is rapidly downregulated during the alternative …
Abstract
The transcription factor CCAAT/enhancer binding protein α (C/EBPα) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBPα 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/EBPα 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/EBPα 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/EBPα in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBPα serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes.
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