Regulation of Hematopoietic Stem Cells in the Osteoblastic Niche
Tissue stem cells are characterized by their abilities to self-renew and to produce numerous differentiated daughter cells. These two special properties enable stem cells to play a central role in maintaining tissues. Many adult tissue stem cells, including hematopoietic system, skin epidermis, gastrointestinal epithelium, brain, and lung were identified (Fuchs, Tumbar, and Guasch 2004; Moore and Lemischka 2006). The activity of tissue stem cells is crucial for supplying the mature cells in normal tissue turnover. It now clear that the stem cell niche regulates the stem cell-specific properties, including self-renewal activity, multi-potentiality, and relative quiescence (Suda, Arai, and Hirao 2005; Adams and Scadden 2006; Wilson and Trumpp 2006). Interaction of stem cells with stem cell niches is critical for maintaining the stem cell properties, including self-renewal capacity and the ability of differentiation into single or multiple lineages.
Hematopoietic stem cells (HSCs) are responsible for blood cell production throughout the lifetime of individual. BM HSCs are best-characterized stem cells. A small subset of HSCs is isolated by cell surface markers (Spangrude, Heimfeld, and Weissman 1988; Osawa, Hanada, Hamada, et al. 1996). These HSCs differentiate into myeloid cells, B cells, and T cells in the presence of various cytokines (Akashi, Traver, Miyamoto, and Weissman 2000). It has been reported that single purified HSC is able to reconstitute lethally irradiated mice (Osawa, Hanada, Hamada, et al.; Matsuzaki, Kinjo, Mulligan, et al. 2004). In contrast to the identification of HSCs, the localization of HSCs in situ and structure of HSC niche had not been solved. Recently, long-term bone marrow (BM) repopulating (LTR) HSCs have been found in BM trabecular bone surface, and it was clarified that an osteoblastic (OB) cell is a critical component for sustaining HSCs (Calvi, Adams, Weibrecht, et al. 2003; Zhang, Niu, Ye, et al. 2003). Long-term label retaining cell (LRC) study showed that 89 % of CD45+Lin- LRCs attached to the endosteal surface (Zhang, Niu, Ye, et al. 2003). It suggests that quiescent/slow-dividing HSCs exclusively located in the osteoblastic niche. HSCs keep a balance between quiescence and cell division/proliferation in the osteoblastic niche (Arai, Hirao, Ohmura, et al. 2004). The specific properties of HSC are controlled dynamically by the signalings of receptor/ligand and cell adhesion molecules produced by osteoblastic niche cells (Suda, Arai, and Hirao 2005; Wilson and Trumpp 2006).
We described here the characterization of HSC and their niche, and the environmental regulation of HSCs in the niche.
KeywordsAtaxia Telangiectasia Mutate Stem Cell Niche Adult Bone Marrow Tie2 Receptor Tissue Stem Cell
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