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.
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.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
-
Lai, A. Y., Watanabe, A., O'Brien, T., Kondo, M.
(2009). Pertussis toxin-sensitive G proteins regulate lymphoid lineage specification in multipotent hematopoietic progenitors. Blood
113: 5757-5764
[Abstract]
[Full Text]
-
Wang, Z., Li, G., Tse, W., Bunting, K. D.
(2009). Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement. Blood
113: 4856-4865
[Abstract]
[Full Text]
-
Singh, K. P., Wyman, A., Casado, F. L., Garrett, R. W., Gasiewicz, T. A.
(2009). Treatment of mice with the Ah receptor agonist and human carcinogen dioxin results in altered numbers and function of hematopoietic stem cells. Carcinogenesis
30: 11-19
[Abstract]
[Full Text]
-
Chabanon, A., Desterke, C., Rodenburger, E., Clay, D., Guerton, B., Boutin, L., Bennaceur-Griscelli, A., Pierre-Louis, O., Uzan, G., Abecassis, L., Bourgeade, M.-F., Lataillade, J.-J., Le Bousse-Kerdiles, M.-C.
(2008). A Cross-Talk Between Stromal Cell-Derived Factor-1 and Transforming Growth Factor-{beta} Controls the Quiescence/Cycling Switch of CD34+ Progenitors Through FoxO3 and Mammalian Target of Rapamycin. Stem Cells
26: 3150-3161
[Abstract]
[Full Text]
-
Nie, Y., Han, Y.-C., Zou, Y.-R.
(2008). CXCR4 is required for the quiescence of primitive hematopoietic cells. JCB
181: i2-i2
[Full Text]