Submitted June 1, 2006
Accepted August 9, 2006
Sustained alterations in biodistribution of stem/progenitor cells in Tie2Cre+
4f/f mice are hematopoietic cell autonomous
Gregory V. Priestley, Tatiana Ulyanova, and Thalia Papayannopoulou*
Department of Medicine/Division of Hematology, University of Washington, Seattle, WA
* Corresponding author; email: thalp{at}u.washington.edu.
We have generated Tie2 Cre+
4f/f mice with documented 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 ones seen with Tie2Cre+VCAM-1f/f mice. To test whether phenotypic differences are due to contributions by other than VCAM-1 ligands in BM, or to we have generated Tie2 Cre+4f/f mice with documented 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 ones seen with Tie2Cre+VCAM-1f/f mice. To test whether phenotypic differences are due to contributions by other than VCAM-1 ligands in BM, or to 4-deficient endothelial cells or pericytes, we carried out transplantation experiments using these mice as donors or as recipients. Changes in progenitor biodistribution post- transplantation were seen only with 4-deficient donor cells, suggesting that these cells were necessary and sufficient to reproduce the phenotype with no discernable contribution by a 4-deficient nonhematopoietic cells. As several similarities post-transplantation are seen between our results and those with CXCR4-/- donor cells, the data suggest that, VLA4/VCAM-1 and CXCF4/CXCL12 pathways contribute to a non-redundant, ongoing signaling required for BM retention of progenitor cells during homeostasis.
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