Article

Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signalling in Bone Marrow Stromal Cell Niches

Department of Medical Systems Control, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Immunity (Impact Factor: 21.56). 01/2007; 25(6):977-88. DOI: 10.1016/j.immuni.2006.10.016
Source: PubMed

ABSTRACT

In the bone marrow, the special microenvironment niches nurture a pool of hematopoietic stem cells (HSCs). Many HSCs reside near the vasculature, but the molecular regulatory mechanism of niches for HSC maintenance remains unclear. Here we showed that the induced deletion of CXCR4, a receptor for CXC chemokine ligand (CXCL) 12 in adult mice, resulted in severe reduction of HSC numbers and increased sensitivity to myelotoxic injury, although it did not impair expansion of the more mature progenitors. Most HSCs were found in contact with the cells expressing high amounts of CXCL12, which we have called CXCL12-abundant reticular (CAR) cells. CAR cells surrounded sinusoidal endothelial cells or were located near the endosteum. CXCL12-CXCR4 signaling plays an essential role in maintaining the quiescent HSC pool, and CAR cells appear to be a key component of HSC niches, including both vascular and endosteal niches in adult bone marrow.

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    • "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]. "
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    • "CXCL12 is a key niche factor that regulates HSC retention in the niche on the one hand and HSC quiescence and multilineage potential [21]. Deletion of CXCR4, the receptor for CXCL12, results in a substantial loss of HSC and demonstrates an essential role of CXCL12-CXCR4 signaling in maintaining HSC quiescence [22]. Furthermore Notch-and Wnt/í µí»½-catenin signaling as well as TGF-í µí»½ signaling pathways are discussed to be important regulators of HSC function. "
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    • "The perivascular MSC are closely related to pericytes as suggested by the detection of the pericyte marker neuron/glial antigen 2 (NG2) [2]. Perivascular MSC subpopulations expressing variable amounts of PDGFRa or CD140a, CD51, Sca-1, leptin receptor (LEP-R), nestin (Nes), and CD146 are considered to be important cellular players of the stem cell niche [2] [5] [6] [14] [16]. It has been reported that 60% of HSCs are directly associated with the vasculature [2] "
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