Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation
Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation
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DOI：
10.1016/s1074-7613(02)00501-0
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发表时间：
2003-01-01
期刊：
影响因子：
32.4
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Hock, H;Hamblen, MJ;Orkin, SH
我们报道了锌指转录因子Gfi - 1在髓系发育中的重要作用。基因靶向的Gfi - 1（-/-）小鼠缺乏正常的中性粒细胞，并且对革兰氏阳性细菌引起的脓肿形成高度敏感。停滞的、形态不典型的Gr1（+）Mac1（+）髓系细胞随着年龄增长在骨髓中扩增。编码初级而非二级或三级中性粒细胞（粒细胞）颗粒蛋白的RNA得以表达。这种不典型的Gr1（+）Mac1（+）细胞群具有中性粒细胞和巨噬细胞谱系的特征，并表现出吞噬作用和呼吸爆发活性。在体外对分选的Gfi - 1（-/-）祖细胞重新表达Gfi - 1可挽救其对G - CSF的中性粒细胞分化反应。因此，Gfi - 1不仅促进中性粒细胞的分化，还拮抗替代的单核细胞/巨噬细胞程序的特性。
We report essential roles of zinc finger transcription factor Gfi-1 in myeloid development. Gene-targeted Gfi-1(-/-) mice lack normal neutrophils and are highly susceptible to abscess formation by gram-positive bacteria. Arrested, morphologically atypical, Gr1(+)Mac1(+) myeloid cells expand with age in the bone marrow. RNAs encoding primary but not secondary or tertiary neutrophil (granulocyte) granule proteins are expressed. The atypical Gr1(+)Mac1(+) cell population shares characteristics of both the neutrophil and macrophage lineages and exhibits phagocytosis and respiratory burst activity. Reexpression of Gfi-1 in sorted Gfi-1(-/-) progenitors ex vivo rescues neutrophil differentiation in response to G-CSF. Thus, Gfi-1 not only promotes differentiation of neutrophils but also antagonizes traits of the alternate monocyte/macrophage program.