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Expression and function of receptors for stem cell factor and
erythropoietin during lineage commitment of human hematopoietic progenitor
cells
J Olweus, LW Terstappen, PA Thompson and F Lund-Johansen
Becton Dickinson Immunocytometry Systems, San Jose, CA 95131-1807, USA.
The aim of the present study was to determine whether stem cell factor
(SCF) and erythropoietin (EPO) act differently on defined subsets of
progenitor cells, and if potential differences correlate with the receptor
density on each subset. To investigate this possibility directly, we
optimized conditions for the identification and purification of homogeneous
progenitor cell subpopulations from human bone marrow. Populations
containing 40% and 44% colony forming cells (CFCs) with 99% and 95% purity
for the granulomonocytic and erythroid lineage, respectively, were sorted
on the basis of differential expression of CD34, CD64, and CD71. In
addition, a population containing 67% CFCs, of which 29-43% were CFU-MIX,
was sorted from CD34hi CD38loCD50+ cells. Purified progenitor cell subsets
were compared directly for responsiveness to SCF and EPO using a short-term
proliferation assay. Expression of the receptors for SCF and EPO were then
examined on each subset using a flow cytometer modified for high-
sensitivity fluorescence measurements. The results show that EPO induces
extensive proliferation of erythroid progenitor cells, but has no effect on
the proliferation or survival of primitive or granulomonocytic progenitors,
even when used in combination with other cytokines. The majority of
erythroid progenitor cells furthermore stained positively with anti-EPO
receptor (EPO-R) monoclonal antibodies, whereas other progenitor cells were
negative. SCF alone induced extensive proliferation of erythroid progenitor
cells, and had a stronger synergistic effect on primitive than on
granulo-monocytic progenitors. In spite of these differences in SCF
activity, there were no significant differences in SCF-R expression between
the progenitor subsets. These results suggest that the selective action of
EPO on erythropoiesis is determined by lineage-restricted receptor
expression, whereas there are additional cell-type specific factors that
influence progenitor cell responses to SCF.
Volume 88,
Issue 5,
pp. 1594-1607,
09/01/1996
Copyright © 1996 by The American Society of Hematology
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