Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages
Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages
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DOI：
10.1182/blood.v97.5.1298
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发表时间：
2001-03-01
期刊：
影响因子：
20.3
通讯作者：
Liebermann, DA
中科院分区：
文献类型：
--
作者：
Krishnaraju, K;Hoffman, B;Liebermann, DA
使用各种分化诱导的骨髓细胞系，我们以前表明，锌指转录因子早期生长反应基因1（Egr-1）是一个积极的调节巨噬细胞分化和负调节粒细胞分化。本研究采用高效逆转录病毒转导技术，在富含骨髓或干细胞的骨髓培养物中异位表达Egr-1，以探讨其对体外和致死剂量照射小鼠造血祖细胞发育的影响。发现正常造血祖细胞中的异位Egr-1表达刺激沿着巨噬细胞谱系的发育，而以沿着粒细胞或红细胞谱系的发育为代价，无论使用何种细胞因子。此外，Egr-1通过抑制生长至巨噬细胞发育程序的增殖期来加速巨噬细胞发育。Egr-1以沿着其他谱系的发育为代价来支配巨噬细胞发育的显著能力导致Egr-1感染的造血祖细胞不能重新填充骨髓和脾脏，从而防止致死辐射小鼠的死亡。这些观察结果进一步强调了Egr-1在单核细胞分化和生长抑制中的作用。（血液，2001;97：1298-1305）（C）2001年由美国血液学会。
Using a variety of differentiation-inducible myeloid cell lines, we previously showed that the zinc-finger transcription factor early growth response gene 1 (Egr-1) is a positive modulator of macrophage differentiation and negatively regulates granulocytic differentiation. In this study, high-efficiency retroviral transduction was used to ectopically express Egr-1 in myeloid-enriched or stem cell-enriched bone marrow cultures to explore its effect on the development of hematopoietic progenitors in vitro and in lethally irradiated mice. It was found that ectopic Egr-1 expression in normal hematopoietic progenitors stimulates development along the macrophage lineage at the expense of development along the granulocyte or erythroid lineages, regardless of the cytokine used, Moreover, Egr-1 accelerated macrophage development by suppressing the proliferative phase of the growth-to-macrophage developmental 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 differentiation and growth suppression. (Blood, 2001;97:1298-1305) (C) 2001 by The American Society of Hematology.