Blood, Vol. 94 No. 4 (August 15), 1999:
pp. 1283-1290
A Critical Role for PU.1 in Homing and Long-Term Engraftment by
Hematopoietic Stem Cells in the Bone Marrow
Robert C. Fisher,
Joshua D. Lovelock, and
Edward W. Scott
From the Institute for Human Gene Therapy, University of
Pennsylvania, Philadelphia, PA.
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 erythropoiesis or to contribute
to the lymphoid and myeloid lineages. PU.1/
HPC are unable to respond synergistically to erythropoietin plus stem
cell factor and have reduced expression of c-kit,
which may explain the erythroid defect. Fluorescently labeled,
PU.1/, AA4.1+, fetal liver HPC
were transferred into irradiated recipients, where they demonstrated a
severely impaired ability to home to and colonize the bone marrow.
PU.1/ HPC were found to lack integrins
4 (VLA-4/CD49d), 5 (VLA-5/CD49e), and
CD11b (M). Collectively, this study has shown that PU.1
plays an important role in controlling migration of hematopoietic
progenitors to the bone marrow and the establishment of long-term
multilineage hematopoiesis.
