LOSS OF FLK-2 FLT3 EXPRESSION DURING COMMITMENT OF MULTIPOTENT MOUSE HEMATOPOIETIC PROGENITOR CELLS TO THE MAST-CELL LINEAGE/

The expression of c-kit and flk-2/flt3 was analyzed in various stages of mast cell differentiation using reverse transcriptase polymerase ch ain reaction (RT-PCR). Mouse fetal liver cells were sorted using antib odies for Sca-1 (Ly6A/E) and CD43 to obtain a population enriched for early progenitors; committed mast cell progenitors were absent from th is population. Mouse fetal liver-derived, IL-3-dependent blast cell co lonies provided a source of committed mast cell progenitors, and mast cell colonies provided mature mast cells. Comparison of these populati ons showed that some uncommitted cells express both c-kit and flk-2/fl t3. At the time of commitment to the mast cell lineage, the expression of c-kit increases compared to that of uncommitted progenitors, and t he expression of flk2/flt3 becomes undetectable. Previous studies have shown that steel factor, the ligand for c-kit, supports mast cell dif ferentiation in vivo and in vitro. In contrast, the ligand for flk-2/f lt3 is inactive on mast cells. Thus, receptor gene expression appears to be an important determinant of the response or lack of response of mast cells to the ligands for these two homologous receptors.