The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells.
Previously we have shown that the zinc finger transcription factor Egr-1 is essential for and restricts differentiation of hematopoietic cells along the macrophage lineage, raising the possibility that Egr-1 actually plays a deterministic role in governing the development of hematopoietic precursor cells along the monocytic lineage. To test this hypothesis, we have taken advantage of interleukin-3-dependent 32Dcl3 hematopoietic precursor cells which, in addition to undergoing granulocytic differentiation in response to granulocyte colony-stimulating factor, were found to be induced for limited proliferation, but not differentiation, by granulocyte-macrophage colony-stimulating factor. It was shown that ectopic expression of Egr-1 blocked granulocyte colony-stimulating factor-induced terminal granulocytic differentiation, consistent with previous findings. In addition, ectopic expression of Egr-1 endowed 32Dcl3 cells with ability to be induced by granulocyte-macrophage colony-stimulating factor for terminal differentiation exclusively along the macrophage lineage. Thus, evidence that Egr-1 potentiates terminal macrophage differentiation has been obtained, suggesting that Egr-1 plays a deterministic role in governing the development of hematopoietic cells along the macrophage lineage.
Krishnaraju
K
K
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Nguyen
H Q
HQ
Liebermann
D A
DA
Hoffman
B
B
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017874:Immediate-Early Proteins; D007377:Interleukin-3 / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D007377:Interleukin-3; D012333:RNA, Messenger; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor