Shear stress, cyclic strain, and material stiffness are known to affect gene expression of differentiated cells and stem cells. Our work has identified gene expression signatures of mesenchymal stem cells (MSCs) that both overlap and are distinct from mature vascular cell types. Mechanosignaling responses were measured in response to both applied shear stress and applied cyclic strain. We identified a network of genes whose expression depends on applied shear stress in MSCs and endothelial cells, and demonstrated this network converges to regulate specific cell functions via conserved mechanosignaling responses.