Article

CXCR4 is required for the quiescence of primitive hematopoietic cells. J Exp Med

Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Journal of Experimental Medicine (Impact Factor: 12.52). 05/2008; 205(4):777-83. DOI: 10.1084/jem.20072513
Source: PubMed

ABSTRACT

The quiescence of hematopoietic stem cells (HSCs) is critical for preserving a lifelong steady pool of HSCs to sustain the highly regenerative hematopoietic system. It is thought that specialized niches in which HSCs reside control the balance between HSC quiescence and self-renewal, yet little is known about the extrinsic signals provided by the niche and how these niche signals regulate such a balance. We report that CXCL12 produced by bone marrow (BM) stromal cells is not only the major chemoattractant for HSCs but also a regulatory factor that controls the quiescence of primitive hematopoietic cells. Addition of CXCL12 into the culture inhibits entry of primitive hematopoietic cells into the cell cycle, and inactivation of its receptor CXCR4 in HSCs causes excessive HSC proliferation. Notably, the hyperproliferative Cxcr4(-/-) HSCs are able to maintain a stable stem cell compartment and sustain hematopoiesis. Thus, we propose that CXCR4/CXCL12 signaling is essential to confine HSCs in the proper niche and controls their proliferation.

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Available from: Yong-Rui Zou
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    • "SDF-1 is highly expressed in the bone marrow by various stromal cells including osteoblasts, endothelial cells, and perivascular reticular cells (Lapidot et al., 2005; Sugiyama et al., 2006). Notably, SDF-1 is also involved in other stem cell functions including regulation of cell quiescence and survival (Nie et al., 2008; Sugiyama et al., 2006). Our data suggest that extremely high levels of SDF-1 in the dermis might be required for skin homeostasis, including epidermal turnover and morphogenesis. "
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    • "CXCR4 is normally expressed by most leukocytes and has one ligand, CXCL12 (Bachelerie et al., 2014; Bleul et al., 1996), which is constitutively expressed at high levels by stromal cells in the bone marrow and normally mediates HSC retention in bone marrow niches (Broxmeyer et al., 2003b; Broxmeyer et al., 2005; Dar et al., 2006; Sugiyama et al., 2006; Zou et al., 1998). In addition, CXCR4 signaling promotes hematopoietic stem cell (HSC) quiescence, homing to bone marrow from blood and differentiation into committed myeloid progenitors (Broxmeyer et al., 2003a, 2003b; Kawai et al., 2007; Nie et al., 2008; Sugiyama et al., 2006). Chromothripsis refers to multiple clustered genetic rearrangements and deletions affecting one or a few chromosomes (Stephens et al., 2011). "
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