Differential Expression of Receptors for Hemopoietic Growth Factors on Subsets of CD34+Hemopoietic Cells

Abstract

The production of peripheral blood cells is regulated by hemopoietic growth factors (HGF) which promote the survival of stem cells and stimulate the proliferation and maturation of progenitors as well as effector functions of mature blood cell subsets. The actions of HGF's are determined by the cellular distribution of receptors for these HGF's within the hemopoietic tissues and by the functional program that receptor-expressing cells can execute after growth factor stimulation. Identification of stem cells and their progeny and delineation of the growth factor receptor phenotype of these cells will establish target cell range and functions of individual growth factors in hemopoiesis. Cells with specific HGF receptors can be detected and isolated by flow cytometric methods, e.g., by staining with biotinylated ligand and fluorescently-tagged streptavidin. Receptor-expressing cells can be classified on the basis of expression of the CD34 antigen and other markers that distinguish immature progenitors from more differentiated cells. Using this approach distinct expression patterns have been shown for the receptors for interleukin-3 (IL-3), IL-6, granulocyte/macrophage colony-stimulating factor (GM-CSF) and Steel Factor (SF) on subsets of CD34+ and CD34- cells in bone marrow. Expression of the IL-3 receptor (R), IL-6R and GM-CSFR appears to be very low on the most immature subsets of CD34+ cells, but increases progressively during successive stages, of in particular myelomonocytic differentiation. In contrast, the receptor for SF, i.e., Kit, is highly expressed on very immature CD34-bright/HLA-DR-dull cells, which include stem cells. Kit levels decline during myelomonocytic and B-lymphoid differentiation whereas they increase to maximal levels during early stages of erythropoiesis. The heterogeneity in receptor expression, together with other immunophenotypic characteristics, allows for the identification of distinct progenitor cell subsets and differentiation stages within the CD34+ cell compartment. By selecting appropriate phenotypic criteria it will be possible to further dissect the stem cell compartment and eventually establish the, possibly heterogeneous, HGF receptor phenotype of pluripotent stem cells.