MafB is an inducer of monocytic differentiation

MafB is an inducer of monocytic differentiation
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DOI:
10.1093/emboj/19.9.1987
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发表时间:
2000-05-02
期刊:
影响因子:
11.4
通讯作者:
Graf, T
Graf, T
中科院分区:
生物学1区
文献类型:
--
作者:
Kelly, LM;Englmeier, U;Graf, T

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bZip 转录因子 MafB 在造血系统的骨髓谱系中特异性表达,并在从多能祖细胞向巨噬细胞的骨髓分化过程中连续上调。在这里,我们报告这种诱导反映了 MafB 在早期骨髓和单核细胞分化中的重要作用。我们观察到,转化鸡造血前体细胞中 MafB 的表达显着增加了骨髓集落形成的比例,但以多能祖细胞型集落为代价。此外,根据形态、表面标记表达和功能标准判断,转化的成髓细胞中 MafB 的过度表达会刺激巨噬细胞的快速形成。 MafB 诱导的巨噬细胞在被脂多糖激活后表现出典型水平的吞噬活性和一氧化氮释放,相比之下?这些细胞中骨髓转录因子 PU.1 的过度表达不会诱导巨噬细胞分化。此外,MafB 的显性失活等位基因抑制骨髓集落形成和成髓细胞向巨噬细胞的分化。综上所述,我们的结果表明 MafB 诱导是造血细胞中单核细胞程序的特定且重要的决定因素。
The bZip transcription factor MafB is expressed specifically in the myeloid lineage of the hematopoietic system and is up-regulated successively during myeloid differentiation from multipotent progenitors to macrophages. Here we report that this induction reflects an essential role of MafB in early myeloid and monocytic differentiation. We observed that the expression of MafB in transformed chicken hematopoietic precursors dramatically increases the proportion of myeloid colony formation at the expense of multipotent progenitor-type colonies. In addition, the overexpression of MafB in transformed myeloblasts stimulates the rapid formation of macrophages, as judged by morphology, surface marker expression and functional criteria. MafB-induced macrophages exhibit typical levels of phagocytic activity and nitric oxide release after activation by lipopolysaccharide, By contrast? overexpression of the myeloid transcription factor PU.1 in these cells does not induce macrophage differentiation. Furthermore, a dominant-negative allele of MafB inhibits both myeloid colony formation and the differentiation of myeloblasts into macrophages. Taken together, our results indicate that MafB induction is a specific and essential determinant of the monocytic program in hematopoietic cells.