CYTOKINE RECEPTOR EXPRESSION ON HEMATOPOIETIC STEM AND PROGENITOR CELLS

Hematopoietic stem and progenitor cell populations were obtained by fl uorescence activated cell sorting of murine bone marrow (BM) cells int o Rhodamine-123(lo) lineage (-)Ly6A/E(+) c-kit(+) (primitive stem cell s highly enriched for long-term BM repopulating activity), Rhodamine-1 23(med/hi) lineage(-) Ly6A/E(+) c-kit(+) (mature stem cells highly enr iched for shortterm BM repopulating activity and day 13 spleen colony- forming activity) and lineage(-) Ly6A/E(-) c-kit(+) (enriched for in v itro colony forming cells) populations. Neither stem cell population r esponds to single cytokines in vitro and each requires the synergistic action of two or more cytokines for proliferation, whereas the progen itor cell population proliferates in response to single cytokines. Sin ce each of these cell populations was sorted as c-kit(+), they express receptors for stem cell factor. Cell populations were also analyzed b y autoradiography for their ability to specifically bind iodinated cyt okines and this revealed that both stem cell populations expressed rec eptors for interIeukin-1 alpha (IL-1 alpha), IL-3, IL-6, and granulocy te colony-stimulating factor (G-CSF), but lacked receptors for macroph age colony-stimulating factor (M-CSF), granulocyte-macrophage colony s timulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Cell s within the progenitor cell population specifically bound IL-3, GM-CS F, G-CSF, IL-6, and IL-1 alpha, whereas no receptors were detected for M-CSF and LIF. Within each cell population examined, heterogeneity wa s observed in the percentage of cells labeled and the number of recept ors 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 distinct ive functional properties. (C) 1997 by The American Society of Hematol ogy.