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Human primitive hematopoietic progenitor cells are more enriched in KITlow
cells than in KIThigh cells
Y Gunji, M Nakamura, H Osawa, K Nagayoshi, H Nakauchi, Y Miura, M Yanagisawa and T Suda
Department of Pediatrics and Medicine, Jichi Medical School, Tochigi- ken,
Japan.
To clarify the phenotypes of various classes of human hematopoietic
progenitor cells, we used a multicolor staining protocol in conjunction
with CD34 and a newly developed mouse antihuman c-kit proto-oncogene
product (KIT) monoclonal antibody (MoAb). We characterized three cell
fractions in CD34+ cells that express KITlow and KIThigh cells in addition
to KIT- cells. A clonogenic assay showed that most granulocyte- macrophage
colony-forming cells (GM-CFC) were present in CD34+KIThigh populations,
whereas erythroid burst-forming cells (BFU-E) were detected mainly in the
CD34+KITlow population. CD34(+)-KIT- fraction contained a small number of
BFU-E. Morphologic analysis showed that blast-like cells were more enriched
in the CD34+KITlow fraction. KITlow cells contained CD34+CD38- cells that
were considered to be very primitive progenitor cells, as determined by a
replating assay. To clarify the biologic differences between both
fractions, we examined the more primitive progenitor cell functions by
assessing long-term culture-initiating cells (LTC-IC) on the stromal cells.
At week 2, more CFC recovered from the culture in the fraction initiated
with a CD34+KIThigh population. However, more LTC-IC were present during
weeks 5 to 9 in the CD34+KITlow population. These results indicate that
primitive progenitors are more enriched in the KITlow population and that
the KIThigh population contains many GM-committed progenitor cells. We also
showed that anti-KIT MoAb inhibited the ability of CD34+ cells to generate
CFC on the stromal layer in the LTC system. This suppressive effect was
more evident in the generation of BFU-E by CD34+KITlow cells. Moreover, we
confirmed that CD34+KIThigh cells emerged from CD34+KITlow cells during
coculture with allogeneic stromal cells or from liquid culture in the
presence of stem cell factor (SCF), interleukin-6, and erythropoietin.
These results emphasize the pivotal role of the KIT and SCF interaction in
hematopoiesis and indicate that KITlow cells are more primitive than
KIThigh cells.
Volume 82,
Issue 11,
pp. 3283-3289,
12/01/1993
Copyright © 1993 by The American Society of Hematology
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