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


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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    • "The location and composition of the HSC niche are areas of intense debate in the stem cell field with numerous studies describing the niche in the mouse (Ellis et al., 2011; Kiel et al., 2005; Nombela-Arrieta et al., 2013; Zhang et al., 2003; Sugiyama et al., 2006; Méndez-Ferrer et al., 2010; Calvi et al., 2003), human trephine sections (Guezguez et al., 2013), and zebrafish (Tamplin et al., 2015). However, although a recent publication described changes in motility of HSPC in the context of parasitic infection (Rashidi et al., 2014), there is very little published information regarding the dynamics of HSPC migration in vivo and how this correlates with functionality. "
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    ABSTRACT: Despite advances in our understanding of interactions between mouse hematopoietic stem cells (HSCs) and their niche, little is known about communication between human HSCs and the microenvironment. Using a xenotransplantation model and intravital imaging, we demonstrate that human HSCs display distinct motile behaviors to their hematopoietic progenitor cell (HPC) counterparts, and the same pattern can be found between mouse HSCs and HPCs. HSCs become significantly less motile after transplantation, while progenitor cells remain motile. We show that human HSCs take longer to find their niche than previously expected and suggest that the niche be defined as the position where HSCs stop moving. Intravital imaging is the only technique to determine where in the bone marrow stem cells stop moving, and future analyses should focus on the environment surrounding the HSC at this point.
    Stem Cell Reports 10/2015; 5(5). DOI:10.1016/j.stemcr.2015.09.003 · 5.37 Impact Factor
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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(4). 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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    ABSTRACT: Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches. Copyright © 2015. Published by Elsevier Ltd.
    Biomaterials 08/2015; 61:103 - 114. DOI:10.1016/j.biomaterials.2015.04.057 · 8.56 Impact Factor
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