Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironment in CXCR4-/- chimeric mice.
The physiologic role of CXCR4 on hematopoietic stem/progenitor cells (HSPCs) 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 with 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 units (CFUs-S), and Lin- Sca-1+ c-kit+ cells in E14.5 CXCR4-/- and CXCR4+/+ livers. In addition, the homing of HSPCs 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.
Foudi
Adlen
A
INSERM U362, IFR54, Institut Gustave Roussy, Villejuif Cedex, France.
Jarrier
Peggy
P
Zhang
Yanyan
Y
Wittner
Monika
M
Geay
Jean-Francois
JF
Lecluse
Yann
Y
Nagasawa
Takashi
T
Vainchenker
William
W
Louache
Fawzia
F
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002465:Cell Movement; D004622:Embryo, Mammalian; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019718:Receptors, CXCR4; D013154:Spleen / Q000166:cytology; D014916:Whole-Body Irradiation
D019718:Receptors, CXCR4