Stem cell factor supports survival of granulocyte progenitors in mouse bone marrow cultures

The regulation of cell differentiation and cell death is crucial to the gen eration of hematopoietic cells both in vitro and in vivo. The biologic role of stem cell factor (SCF) in hematopoietic cell development is not well kn own. We monitored the survival, proliferation and differentiation of mouse hematopoietic cells in culture in the presence of SCF Examination of colony formation, MTT and thimidine killing of mouse bone marrow indicated that S CF is mainly a survival factor. Our results show that SCF maintains cells i n a "undifferentiated" state. Committed granulocytic and monocytic progenit ors (CFU-GM) survive for seven days in the presence of SCF alone, under con ditions where no maturing granulocytic monocytic cells could be recovered. On transfer to GM-CSF containing cultures, these cells proliferate and diff erentiate terminally. Together, our data indicate that SCF induces survival in hematopoietic progenitors. Furthermore, SCF favors the survival of gran ulocytic progenitors over that of monocytic progenitors. In the absence of later acting factors such as CM-CSF, cells that progress beyond the CFU-GM stage loose c-kit expression and die by default. Hence, tack of cell expans ion in the presence of SCF by itself is due to constant cell proliferation and survival, which is counterbalanced by cell death. In contrast, the pres ence of both SCF and GM-CSF allows for the continuous survival and expansio n of hematopoietic progenitor cells in culture, as well as favoring their t erminal differentiation along granulocytic and monocytic pathways. Furtherm ore, CM-CSF induces colonies of macrophages that produce G-CSF and IL-6, tw o molecules involved in granulopoiesis, and these in turn stimulate granulo cyte colony formation. Finally, our data suggest that survival signals by S CF are crucial during the differentiative process of granulocytes, giving s trength to deterministic model.