Objective. Three GATA family transcription factors are involved in various
aspects of hematopoiesis. Their lineage-restricted expression correlates we
ll with their function in selective lineage commitment and differentiation.
We focused on the role of GATA-3 to determine whether an intrinsic variati
on among different GATA proteins, in addition to the distinct expression pa
ttern, determines lineage specification.
Materials and Methods. Using a retroviral vector, we introduced the GATA-3
gene into primary murine hematopoietic stem cells (HSC) and examined their
development in in vitro suspension culture and colony-forming assays as wel
l as in vivo competitive repopulation studies.
Results. Although GATA-3 expression normally is restricted to lymphoid prec
ursor and committed T cells, overexpression of GATA-3 in HSC results in ces
sation of cell expansion followed by selective induction of megakaryocytic
and erythroid differentiation and inhibition of myeloid and lymphoid precur
sor development in liquid suspension culture and in vitro colony-forming as
says. Competitive repopulation studies show that transplanted GATA-3-expres
sing HSC/progenitor cells give one wave of erythrocyte development but fail
to expand in the bone marrow or to reconstitute other lineages.
Conclusions. The selective megakaryocytic/erythroid differentiation in HSC
with enforced GATA-3 expression suggests a functional redundancy among GATA
proteins and indicates that the specific lineage fate determination by ind
ividual GATA proteins is largely regulated at the level of expression in a
lineage and developmental-stage restricted fashion, whereas the identity of
the GATA factor may not be as important. (C) 2001 International Society fo
r Experimental Hematology. Published by Elsevier Science Inc.