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 in terleukin-3 (IL-3)-dependent, multipotent hemopoietic cell line allowe d these cells to survive in the absence of IL-3, both in serum-contain ing and serum-deprived conditions, and this survival was accompanied b y multilineage differentiation. Moreover, single cell experiments show ed that differentiation could occur in the absence of cell division. W hile these data do not rule out the possibility that growth factors ca n influence the lineage choice of multipotent cells, they suggest that exposure to growth factors may not be obligatory for the differentiat ion of stem cells. The data also support the hypothesis that different iation is intrinsically determined and that the role of the hemopoieti c growth factors is enabling rather than inductive.