The differentiation program of embryonic definitive hematopoietic stem cells is largely α-4 integrin independent

Previous analyses of the roles of alpha 4 integrins in hematopoiesis by other groups have led to conflicting evidence. alpha 4 integrin mutant cells developing in [alpha 4 integrin(-/-): wt] chimeric mice are not capable of completing lymphomyeloid differentiation, whereas conditional inactivation of alpha 4 integrin in adult mice has only subtle effects. We show here that circumventing the fetal stage of hematopoietic stem cell (HSC) development by transplantation of embryonic alpha 4 integrin(-/-) cells into the adult microenvironment results in robust and stable long-term generation of alpha 4 integrin(-/-) lymphoid and myeloid cells, although colonization of Peyer patches and the peritoneal cavity is significantly impaired. We argue here that collectively, our data and the data from other groups suggest a specific requirement for alpha 4 integrin during the fetal/neonatal stages of HSC development that is essential for normal execution of the lymphomyeloid differentiation program.