Fetal and Adult Hematopoietic Stem Cells Require β1 Integrin Function for Colonizing Fetal Liver, Spleen, and Bone Marrow

AbstractHoming 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 β1 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 β1 integrin null HSCs isolated from mice carrying loxP-tagged β1 integrin alleles and ablated for β1 integrin expression by retroviral cre transduction failed to engraft irradiated recipient mice. Moreover, absence of β1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define β1 integrin as an essential adhesion receptor for the homing of HSCs