title: Sustained alterations in biodistribution of stem/progenitor cells in Tie2Cre+ alpha4(f/f) mice are hematopoietic cell autonomous.
abstract: We have generated Tie2Cre+alpha4(f/f) mice with documented alpha4-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-1(f/f) mice. To test whether phenotypic differences are due to contributions by ligands other than VCAM-1 in bone marrow, or to alpha4-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 alpha4-deficient donor cells, suggesting that these cells were necessary and sufficient to reproduce the phenotype with no discernible contribution by alpha4-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.
authors.affiliation: Division of Hematology, Department of Medicine, Box 357710, Seattle, WA 98195, USA.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Priestley
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ulyanova
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D039001:Integrin alpha Chains / Q000172:deficiency / Q000235:genetics; D039041:Integrin alpha4beta1 / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D020286:Pericytes / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011828:Radiation Chimera; D042787:Receptor, TIE-2 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
chemical_list: C063493:CDw49d; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D039001:Integrin alpha Chains; D039041:Integrin alpha4beta1; D008024:Ligands; D019718:Receptors, CXCR4; D019010:Vascular Cell Adhesion Molecule-1; D042787:Receptor, TIE-2; C045073:Cre recombinase; D019426:Integrases