SPECIFIC SIGNALS GENERATED BY THE CYTOPLASMIC DOMAIN OF THE GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) RECEPTOR ARE NOT REQUIRED FOR G-CSF-DEPENDENT GRANULOCYTIC DIFFERENTIATION

Granulocyte colony-stimulating factor (G-CSF) is the principal growth factor regulating the production of neutrophils, yet its role in linea ge commitment and terminal differentiation of hematopoietic progenitor cells is controversial. In this study, we describe a system to study the role of G-CSF receptor (G-CSFR) signals in granulocytic differenti ation using retroviral transduction of G-CSFR-deficient, primary hemat opoietic progenitor cells. We show that ectopic expression of wild-typ e G-CSFR in hematopoietic progenitor cells supports G-CSF-dependent di fferentiation of these cells into mature granulocytes, macrophages, me gakaryocytes, and erythroid cells. Furthermore, we show that two mutan t G-CSFR proteins, a truncation mutant that deletes the carboxy-termin al 96 amino acids and a chimeric receptor containing the extracellular and transmembrane domains of the G-CSFR fused to the cytoplasmic doma in of the erythropoietin receptor, are able to support the production of morphologically mature, chloroacetate esterase-positive, Gr-1/Mac-1 -positive neutrophils in response to G-CSF. These results demonstrate that ectopic expression of the G-CSFR in hematopoietic progenitor cell s allows for multilineage differentiation and suggest that unique sign als generated by the cytoplasmic domain of the G-CSFR are not required for G-CSF-dependent granulocytic differentiation, (C) 1998 by The Ame rican Society of Hematology.