Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages

Using a variety of differentiation-inducible myeloid cell lines, we previou sly showed that the zinc-finger transcription factor early growth response gene 1 (Egr-1) is a positive modulator of macrophage differentiation and ne gatively regulates granulocytic differentiation. In this study, high-effici ency retroviral transduction was used to ectopically express Egr-1 in myelo id-enriched or stem cell-enriched bone marrow cultures to explore its effec t on the development of hematopoietic progenitors in vitro and in lethally irradiated mice. It was found that ectopic Egr-1 expression in normal hemat opoietic progenitors stimulates development along the macrophage lineage at the expense of development along the granulocyte or erythroid lineages, re gardless of the cytokine used, Moreover, Egr-1 accelerated macrophage devel opment by suppressing the proliferative phase of the growth-to-macrophage d evelopmental program. The remarkable ability of Egr-1 to dictate macrophage development at the expense of development along other lineages resulted in failure of Egr-1-infected hematopoietic progenitors to repopulate the bone marrow and spleen, and thereby prevent death, in lethally irradiated mice. These observations further highlight the role Egr-1 plays in monocytic dif ferentiation and growth suppression. (Blood, 2001;97:1298-1305) (C) 2001 by The American Society of Hematology.