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Blood, 1 January 2007, Vol. 109, No. 1, pp. 109-111.
Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2006-06-026427.


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HEMATOPOIESIS

Brief report

Sustained alterations in biodistribution of stem/progenitor cells in Tie2Cre+{alpha}4f/f mice are hematopoietic cell autonomous

Gregory V. Priestley1, Tatiana Ulyanova1, and Thalia Papayannopoulou1,

1 Department of Medicine/Division of Hematology, University of Washington, Seattle

We have generated Tie2Cre+{alpha}4f/f mice with documented {alpha}4-integrin ablation in hematopoietic and endothelial cells. A prominent feature in this model is a sustained, significant increase in circulating progenitors at levels higher than the levels seen with Tie2Cre+VCAM-1f/f mice. To test whether phenotypic differences are due to contributions by ligands other than VCAM-1 in bone marrow, or to {alpha}4-deficient endothelial cells or pericytes, we carried out transplantation experiments using these mice as donors or as recipients. Changes in progenitor biodistribution after transplantation were seen only with {alpha}4-deficient donor cells, suggesting that these cells were necessary and sufficient to reproduce the phenotype with no discernible contribution by {alpha}4-deficient nonhematopoietic cells. Because several similarities are seen after transplantation between our results and those with CXCR4–/– donor cells, the data suggest that VLA4/VCAM-1 and CXCR4/CXCL12 pathways contribute to a nonredundant, ongoing signaling required for bone marrow retention of progenitor cells during homeostasis.


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