Fetal and adult hematopoietic stem cells require β1 integrin function for colonizing fetal liver, spleen, and bone marrow

Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta 1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta 1 integrin null HSCs isolated from mice carrying loxP-tagged beta 1 integrin alleles and ablated for beta 1 integrin expression by retroviral cre transduction failed to engraft irradiated recipient mice. Moreover, absence of beta 1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define beta 1 integrin as an essential adhesion receptor for the homing of HSCs.