The Journal of Experimental Medicine
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Published online March 31, 2008
doi:10.1084/jem.20072513
The Journal of Experimental Medicine, Vol. 205, No. 4, 777-783
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Nie et al.
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BRIEF DEFINITIVE REPORT

CXCR4 is required for the quiescence of primitive hematopoietic cells

Yuchun Nie, Yoon-Chi Han, and Yong-Rui Zou

Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032

CORRESPONDENCE Yong-Rui Zou: yz2001{at}columbia.edu

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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