SUPPRESSION OF APOPTOSIS ALLOWS DIFFERENTIATION AND DEVELOPMENT OF A MULTIPOTENT HEMATOPOIETIC-CELL LINE IN THE ABSENCE OF ADDED GROWTH-FACTORS

In the absence of growth factors, hemopoietic cells die rapidly by the process of apoptosis. Transfection of the human bcl-2 gene into an interleukin-3 (IL-3)-dependent, multipotent hemopoietic cell line allowed these cells to survive in the absence of IL-3, both in serum-containing and serum-deprived conditions, and this survival was accompanied by multilineage differentiation. Moreover, single cell experiments showed that differentiation could occur in the absence of cell division. While these data do not rule out the possibility that growth factors can influence the lineage choice of multipotent cells, they suggest that exposure to growth factors may not be obligatory for the differentiation of stem cells. The data also support the hypothesis that differentiation is intrinsically determined and that the role of the hemopoietic growth factors is enabling rather than inductive.