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: 32.24). 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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    • "Cells were sorted into defined subpopulations with a FACSAria II (BD Biosciences). Total or lineage-negative bone marrow cells were stained and gated according to established methods (Kiel et al., 2005; Oguro et al., 2013; Rathinam et al., 2008, 2011; Yamamoto et al., 2013; Yilmaz et al., 2006). For the CLP assay, total bone marrow cells were stained with a lineage cocktail (CD3, CD11b, GR1, and TER119) and B220 with separate fluorochromes (Karsunky et al., 2008). "
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    Stem Cell Reports 09/2015; 5. DOI:10.1016/j.stemcr.2015.08.006 · 5.37 Impact Factor
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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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    Biomaterials 08/2015; 61:103 - 114. DOI:10.1016/j.biomaterials.2015.04.057 · 8.56 Impact Factor
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