alpha 4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo

We investigated roles of alpha 4 integrins during hematopoiesis using mutan t and chimeric mice. Yolk sac erythropoiesis and migration of hematopoietic progenitors to fetal liver, spleen, and bone marrow can occur without a4 i ntegrins. Although terminal differentiation of these progenitors is possibl e without alpha 4 integrins, these receptors are essential to maintain norm al hematopoiesis in fetal liver, spleen, and bone marrow microenvironments. Moreover, alpha 4-deficient erythroid progenitors and pre-B cells neither transmigrate beneath the stroma nor expand properly in vitro. In contrast, alpha 4-null cells migrate and differentiate efficiently into T lymphocytes within the thymus. In summary, alpha 4 integrins are essential for normal development of ail hematopoietic lineages in fetal liver, bone marrow, and spleen, likely by regulating the proliferation/differentiation balance of h ematopoietic progenitors.