Receptor for macrophage colony-stimulating factor transduces a signal decreasing erythroid potential in the multipotent hematopoietic EML cell line

Objective. To test the hypothesis that hematopoietic growth factors may inf luence lineage choice in pluripotent progenitor cells, we investigated the effects of macrophage colony-stimulating factor QI-CSF) on erythroid and my eloid potentials of multipotent EML cells ectopically expressing M-CSF rece ptor (M-CSFR). Materials and Methods. EML cells are stem cell factor (SCF) dependent murin e cells that give rise spontaneously to pre-B cells, burst-forming unit ery throid (BPU-E), and colony-forming unit granulocyte macrophage (CFU-GM). We determined BFU-E and CFU-GM frequencies among EML cells transduced with mu rine M-CSFR, human M-CSFR, or chimeric receptors, and cultivated in the pre sence of SCF, M-CSF, or both growth factors, Effects of specific inhibitors of signaling molecules were investigated. Results. EML cells transduced with murine M-CSFR proliferated in response t o MI-CSF but also exhibited a sharp and rapid decrease in BFU-E frequency a ssociated with an increase in CFU-GM frequency, In contrast, EML cells expr essing human M-CSFR proliferated in response to RI-CSF without any changes in erythroid or myeloid potential, Using chimeric receptors between human a nd murine,M-CSFR, we shelved that the effects of M-CSF on EML cell differen tiation potential are mediated by a large region in the intracellular domai n of murine M-CSFR. Furthermore, phospholipase C (PLC) inhibitor U73122 int erfered with the negative effects of ligand-activated murine M-CSFR on EML cell erythroid potential, Conclusion. We propose that signaling pathways activated by tyrosine kinase receptors may regulate erythroid potential and commitment decisions in mul tipotent progenitor cells and that PLC may play a keg role in this process, (C) 2000 International Society for Experimental Hematology. Published by E lsevier Science Inc.