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Original Article

^a Department of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California 94305
Dept. of Medicine, Div. of Medical Oncology and Transplantation, Duke University Medical Center, Box 3225<it>,</it> 247A Carl Bldg., Durham, NC 27710.919-681-7060919-668-0249

jos.domen{at}duke.edu

Growth factors can cause cells to proliferate, differentiate, survive, or die. Distinguishing between these responses is difficult in multicellular, multiparameter systems. Yet this is essential to understand the impact on cells like hematopoietic stem cells (HSCs), which have strict and still poorly understood growth factor requirements. Single cell plating in serum-free medium allows direct assessment of growth factor responses. The range of tested factors can be expanded if the cells are protected from growth factor deprivation–induced apoptosis. BCL-2 is overexpressed in HSCs of H2K-BCL-2 transgenic mice, protecting them from many apoptotic stimuli. The response of single wild-type and transgenic HSCs to stimulations with individual factors was tested. Surprisingly, we find that high level BCL-2 expression does not prevent rapid death under serum-free conditions, even though it does in the presence of serum. We also find that transgenic, but not wild-type cells, survive and proliferate rapidly in response to steel factor (Kit ligand). These studies show that two separate signals are necessary to prevent apoptosis in HSCs, and that Kit ligand by itself provides a strong proliferative stimulus to HSCs. However, the proliferative response does not result in self-renewal, but in differentiation to all known hematopoietic oligolineage progenitors.

Key Words: hematopoietic stem cell • transgenic mice • flow cytometry • stem cell factor • serum-free medium

© 2000 The Rockefeller University Press

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