Contribution of α6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with α4 integrins

The integrin a6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. The integrin a6 chain is ubiquitously expressed in human HPCs. Laminin-411 and -511, are present in subendothelial basement membranes of sinusoids in bone marrow, at sites of hematopoietic cell development and trafficking and might, therefore, regulate HSC functions. In this paper, they show that mouse HSC and progenitors express a6B1 integrin which mediates high cell adhesion to laminin-511 and 521 and to laminin-411 to a lower extent. Blocking of a6 significantly reduced progenitor cell homing to bone marrow in mice. Integrin a4 receptors are also important for homing of HSCs to bone marrow (but not to the spleen). The first data showing that a6 integrins (LN521/511 binding) function in vivo as hematopoietic stem and progenitor cell homing receptors. Also, show the role of integrin a4 receptor for homing of long-term multilineage reconstituting HSCs and collaboration of these 2 integrins in homing of short-term HSCs.