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Cytokine receptor expression on hematopoietic stem and progenitor cells
WJ McKinstry, CL Li, JE Rasko, NA Nicola, GR Johnson and D Metcalf
Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Hematopoietic stem and progenitor cell populations were obtained by
fluorescence activated cell sorting of murine bone marrow (BM) cells into
Rhodamine-123io lineage-Ly6A/ E+ c-kit+ (primitive stem cells highly
enriched for long-term BM repopulating activity), Rhodamine- 123med/hl
lineage- Ly6A/E+ c-kit+ (mature stem cells highly enriched for shortterm BM
repopulating activity and day 13 spleen colony-forming activity) and
lineage- Ly6A/E- c-kit+ (enriched for in vitro colony forming cells)
populations. Neither stem cell population responds to single cytokines in
vitro and each requires the synergistic action of two or more cytokines for
proliferation, whereas the progenitor cell population proliferates in
response to single cytokines. Since each of these cell populations was
sorted as c-kit+, they express receptors for stem cell factor. Cell
populations were also analyzed by autoradiography for their ability to
specifically bind iodinated cytokines and this revealed that both stem cell
populations expressed receptors for interleukin-1 alpha (IL-1 alpha), IL-3,
IL-6, and granulocyte colony-stimulating factor (G-CSF), but lacked
receptors for macrophage colony-stimulating factor (M-CSF),
granulocyte-macrophage colony stimulating factor (GM-CSF), and leukemia
inhibitory factor (LIF). Cells within the progenitor cell population
specifically bound IL-3, GM-CSF, G-CSF, IL-6, and IL-1 alpha, whereas no
receptors were detected for M-CSF and LIF. Within each cell population
examined, heterogeneity was observed in the percentage of cells labeled and
the number of receptors per cell. These results suggest that stem cell
populations can be further subdivided according to their cytokine receptor
profile and it will be of interest to determine if such subpopulations have
distinctive functional properties.
Volume 89,
Issue 1,
pp. 65-71,
01/01/1997
Copyright © 1997 by The American Society of Hematology
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