The object of this project is to define the genetic basis for the regulation of mononuclear phagocyte proliferation, differentiation and functional heterogeneity. In addition, we wish to define the role hematopoietic growth factors play in the control of their production from the multipotent hematopoietic stem cell. We will approach this objective by using currently available antibodies to differentiation antigens to identify and sort, using flow cytometry, cells at unique differentiation stages. By culturing these sorted cells in the presence of the selected hematopoietic growth factors IL3, GM-CSF and M-CSF, we will determine their differentiation kinetics. This will be accomplished by using a panel or monoclonal antibodies to define the phenotype of the progeny which emerge as a function of time from the sorted precursors. We will also investigate the expression of proto-oncogene products using currently available antibodies. This expression will be correlated with the proliferation stages of the cells as well as their differentiation stage. In this way, we will be able to determine if the gene's expression is cell cycle related and independent of differentiation, whether its expression is related to differentiation or both. Results of these studies will have an enormous impact on our understanding of how a normal cell's production and function is controlled in health and disease.
