Fetal and adult hematopoietic stem cells require beta1 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 beta1 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 beta1 integrin null HSCs isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for beta1 integrin expression by retroviral cre transduction failed to engraft irradiated recipient mice. Moreover, absence of beta1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define beta1 integrin as an essential adhesion receptor for the homing of HSCs.
Potocnik
A J
AJ
Basel Institute for Immunology, Switzerland. potocnik@bii.ch
Brakebusch
C
C
Fässler
R
R
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000196:embryology / Q000254:growth & development / Q000276:immunology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003114:Colony-Forming Units Assay; D005333:Fetus / Q000276:immunology*; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000502:physiology; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D011828:Radiation Chimera / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000276:immunology*
D019012:Integrin beta1