A critical role for PU.1 in homing and long-term engraftment by hematopoietic stem cells in the bone marrow

We have previously demonstrated that PU.1 is required for the production of lymphoid and myeloid, but not of erythroid progenitors in the fetal liver. In this study, competitive reconstitution assays show that E14.5 PU.1(-/-) hematopoietic progenitors (HPC) fail to sustain definitive/adult erythropo iesis or to contribute to the lymphoid and myeloid lineages. PU.1(-/-) HPC are unable to respond synergistically to erythropoietin plus stem cell fact or and have reduced expression of c-kit, which may explain the erythroid de fect. Fluorescently labeled, PU.1(-/-), AA4.1(+), fetal liver HPC were tran sferred into irradiated recipients, where they demonstrated a severely impa ired ability to home to and colonize the bone marrow. PU.1-/- HPC were foun d to lack integrins alpha(4) (VLA-4/CD49d), alpha(5) (VLA-5/CD49e), and CD1 1b (alpha(M)). Collectively, this study has shown that PU.1 plays an import ant role in controlling migration of hematopoietic progenitors to the bone marrow and the establishment of long-term multilineage hematopoiesis, (C) 1 999 by The American Society of Hematology.