SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells

Howard Hughes Medical Institute and Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Cell (Impact Factor: 33.12). 08/2005; 121(7):1109-21. DOI: 10.1016/j.cell.2005.05.026
Source: PubMed

ABSTRACT To improve our ability to identify hematopoietic stem cells (HSCs) and their localization in vivo, we compared the gene expression profiles of highly purified HSCs and non-self-renewing multipotent hematopoietic progenitors (MPPs). Cell surface receptors of the SLAM family, including CD150, CD244, and CD48, were differentially expressed among functionally distinct progenitors. HSCs were highly purified as CD150(+)CD244(-)CD48(-) cells while MPPs were CD244(+)CD150(-)CD48(-) and most restricted progenitors were CD48(+)CD244(+)CD150(-). The primitiveness of hematopoietic progenitors could thus be predicted based on the combination of SLAM family members they expressed. This is the first family of receptors whose combinatorial expression precisely distinguishes stem and progenitor cells. The ability to purify HSCs based on a simple combination of SLAM receptors allowed us to identify HSCs in tissue sections. Many HSCs were associated with sinusoidal endothelium in spleen and bone marrow, though some HSCs were associated with endosteum. HSCs thus occupy multiple niches, including sinusoidal endothelium in diverse tissues.

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    • "Staining for tartrate resistant acid phosphatase (TRAP, red) B.M. Holzapfel et al. / Biomaterials 61 (2015) 103e114 104 multi-potency and long-term reconstitution [2]. The endosteal [3] [4], mesenchymal [5] [6] and vascular systems [7] have been identified as the main regulating components of the HSC niches, nevertheless the concept of the niche embodies the physical entity of all its single constituents [8]. In the last years, researchers have become more aware of the fact that the niche itself can be a driver for pathogenesis, particularly in bone metastatic disease or leukemia [9] [10]. "
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    • "Here, we showed that phenotypic heterogeneity was present in the resting blood CD34þ cells from LRS chambers. Most CD34þCD45 low cells from peripheral blood were positive for CD38 and CD244, indicating their commitment toward differentiation [48] [56]. In addition, these cells were also positive for the transferrin receptor CD71. "
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    • "During stem cell homing, HSCs expressing CXCR-4 are attracted to the osteoblastic niche, which expresses high levels of SDF-1 (Kopp et al., 2005). HSCs expressing signaling lymphocyte activation molecule markers were detected on the osteoblastic surface of trabecular bone as well as adjacent to sinusoidal ECs (Kiel et al., 2005). Hematopoiesis is severely altered in conditionally transgenic mice, which exhibit osteoblast deficiency (Visnjic et al., 2004). "
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