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.

Download full-text


Available from: Cox Terhorst, Jan 31, 2016
  • Source
    • "Therefore, we speculate that surrounding cells generated by lingual epithelial stem cells could be candidate niche cells. In the bone marrow, several concepts for the hematopoietic stem cell niche were proposed in the 2000s; these include the osteoblastic niche[36], reticular cell niche[37], and perivascular niche[38]. Recently, the arteriolar niche[39]and perisinusoidal niche[40]were also proposed.Yamazaki et al.demonstrated that Schwann cells were components of the perivascular niche and had the ability to induce a dormancy state in hematopoietic stem cells[41]. Based on the concepts of the stem cell niche proposed in various tissues, it is possible that similar niche systems, such as the descendant cell niche, perivasucular niche, mesenchymal niche, and neurogenic niche, also function in the lingual epithelium (Figure 4). "
    [Show abstract] [Hide abstract]
    ABSTRACT: As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP), were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine.
    Preview · Article · Jan 2016 · International Journal of Molecular Sciences
  • Source
    • "At steady state, CD48 is expressed on nearly all hematopoietic cells (Fig. 2)[3,7,19,39,55565758. In fact, the only hematopoietic cell populations in mice that distinctly lack CD48 expression in mice are neutrophils and a subset of long-term hematopoietic stem cells (LT-HSCs)[59,60]. However, in humans CD48 is also found on neutrophils and other HSC types[61,62]Monocytes and lymphocytes have elevated CD48 expression in patients with viral and bacterial infections[61]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: CD48, a member of the signaling lymphocyte activation molecule family, participates in adhesion and activation of immune cells. Although constitutively expressed on most hematopoietic cells, CD48 is upregulated on subsets of activated cells. CD48 can have activating roles on T cells, antigen presenting cells and granulocytes, by binding to CD2 or bacterial FimH, and through cell intrinsic effects. Interactions between CD48 and its high affinity ligand CD244 are more complex, with both stimulatory and inhibitory outcomes. CD244:CD48 interactions regulate target cell lysis by NK cells and CTLs, which are important for viral clearance and regulation of effector/memory T cell generation and survival. Here we review roles of CD48 in infection, tolerance, autoimmunity, and allergy, as well as the tools used to investigate this receptor. We discuss stimulatory and regulatory roles for CD48, its potential as a therapeutic target in human disease, and current challenges to investigation of this immunoregulatory receptor.
    Full-text · Article · Jan 2016 · Clinical Immunology
  • Source
    • "HSCs), short-term hematopoietic stem cells (ST-HSCs), and multipotent progenitors (MPPs) were gated respectively, as Lin -cKit + Sca1 + CD34 -Flt3 -, Lin -cKit + Sca1 + CD34 + Flt3 -, and Lin cKit + Sca1 + CD34 + Flt3 + (Challen et al., 2009). In (E) hematopoietic stem cells (HSCs), and progenitor populations MPP, HPC1 and HPC2 were gated as Lin -cKit + Sca1 + CD150 + CD48 -, Lin -cKit + Sca1 + CD150 - CD48 -, Lin -cKit + Sca1 + CD150 -CD48 + , and Lin -cKit + Sca1 + CD150 + CD48 + (Kiel et al., 2005). Bars show mean ± SEM; * p<0.05, ** p<0.01, *** p<0.001, "

    Full-text · Dataset · Jan 2016
Show more