Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis

Authors
Citation
D. Chen et G. Zhang, Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis, EXP HEMATOL, 29(8), 2001, pp. 971-980
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
EXPERIMENTAL HEMATOLOGY
ISSN journal
0301-472X → ACNP
Volume
29
Issue
8
Year of publication
2001
Pages
971 - 980
Database
ISI
SICI code
0301-472X(200108)29:8<971:EEOTGT>2.0.ZU;2-C
Abstract
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.