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Stem cell factor retards differentiation of normal human erythroid
progenitor cells while stimulating proliferation
K Muta, SB Krantz, MC Bondurant and CH Dai
Department of Medicine, Department of Veterans Affairs Medical Center,
Nashville, TN, USA.
Stem cell factor (SCF), the ligand for the c-kit tyrosine kinase receptor,
markedly stimulates the accumulation of erythroid progenitor cells in
vitro. We now report that SCF delays erythroid differentiation among the
progeny of individual erythroid progenitors while greatly increasing the
proliferation of these progeny. These effects appear to be independent of
an effect on maintenance of cell viability. Highly purified day-6 erythroid
colony-forming cells (ECFC), consisting mainly of colony-forming
units-erythroid (CFU-E), were generated from human peripheral blood
burst-forming units-erythroid (BFU-E). Addition of SCF to the ECFC in
serum-free liquid culture, together with erythropoietin (EP) and
insulin-like growth factor 1 (IGF-1), resulted in a marked increase in DNA
synthesis, associated with a delayed peak in cellular benzidine positivity
and a delayed incorporation of 59Fe into hemoglobin compared with cultures
without SCF. In the presence of SCF, the number of ECFC was greatly
expanded during this culture period, and total production of
benzidine-positive cells plus hemoglobin synthesis were ultimately
increased. To determine the effect of SCF on individual ECFC, single-cell
cultures were performed in both semisolid and liquid media. These cultures
demonstrated that SCF, in the presence of EP and IGF-1, acted on single
cells and their descendants to delay erythroid differentiation while
substantially stimulating cellular proliferation, without an enhancement of
viability of the initial cells. This was also evident when the effect of
SCF was determined using clones of ECFC derived from single BFU-E. Our
experiments demonstrate that SCF acts on individual day-6 ECFC to retard
erythroid differentiation while simultaneously providing enhanced
proliferation by a process apparently independent of an effect on cell
viability or programmed cell death.
Volume 86,
Issue 2,
pp. 572-580,
07/15/1995
Copyright © 1995 by The American Society of Hematology

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