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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2243-2251.
Prepublished online as a Blood First Edition Paper on November 15, 2005; DOI 10.1182/blood-2005-02-0581.
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Submitted February 10, 2005
Accepted October 27, 2005
Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironment in CXCR4-/- chimeric mice
Adlen Foudi, Peggy Jarrier, Yanyan Zhang, Monika Wittner, Jean-Francois Geay, Yann Lecluse, Takashi Nagasawa, William Vainchenker, and Fawzia Louache*
Inserm U362, Institut Gustave Roussy, Villejuif, France
IFR54, Institut Gustave Roussy, Villejuif, France
Department of Medical Systems Control, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
* Corresponding author; email: fawl{at}igr.fr.
The physiological role of CXCR4 on hematopoietic stem/progenitor cells (HSPC) is not fully understood. Here, we show that radioprotection of lethally irradiated mice by embryonic day 14.5 (E14.5) CXCR4-/- fetal liver (FL) cells was markedly impaired when compared to CXCR4+/+ counterparts, but this defect was rescued when hosts were engrafted with high cell numbers. This quantitative defect contrasted with a similar content in hematopoietic colony forming cells (CFCs), splenic colony-forming unit (CFU-S) and Lin- Sca-1+ c-kit+ cells in E14.5 CXCR4-/- and CXCR4+/+ livers. In addition, the homing of HSPC in the bone marrow was not altered as detected with a CFSE-staining assay. In contrast, a 30-fold increase in CFCs was seen in the circulation of mice stably reconstituted with CXCR4-/- FL cells and this increment was already observed before hematopoiesis had reached a steady state level. Together, the data strongly suggest that impaired retention may, at least in short-term hematopoietic reconstitution, lead to a diminution in the number of available progenitors required for radioprotection.
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