Endothelial progenitor cells (EPCs) could function as niche cells to promote self—renewal of mesenchymal stem cells (MSCs) in the mouse bone marrow. Cohesion was the basis of the two cells to display their biological functions to each other. In this study, we investigated the mechanism of cohesion between MSCs and EPCs. And demonstrated that fibronectin (FN) in EPCs activated the integrin α5β1 of MSCs and further mediated cell-cell cohesion. Integrin α5β1 and its FN ligand played critical roles not only in single—cell line adhesion, but also in adhesion between stem and niche cells. This novel finding is important to understand the cross—talk between MSCs and their niche cells.