Identification of three genes up-regulated in PU.1 rescued monocytic precursor cells

Identification of three genes up-regulated in PU.1 rescued monocytic precursor cells
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DOI:
10.1093/intimm/dxf040
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发表时间:
2002-07-01
影响因子:
4.4
通讯作者:
Maki, RA
Maki, RA
中科院分区:
医学3区
文献类型:
--
作者:
Henkel, GW;McKercher, SR;Maki, RA

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转录因子PU.1对巨噬细胞发育的需要已经有很好的记录。然而,PU.1控制巨噬细胞成熟所调控的靶基因尚不清楚。粒细胞巨噬细胞集落刺激因子(GM-CSF)依赖性PU.1空单核细胞前体细胞稳定转导的PU.1表达逆转录病毒。PU.1的表达改变了单核细胞上表达的一些蛋白质的表面表达;然而,这些细胞仍然依赖GM-CSF并保持不成熟的表型。与PU.1无效细胞相反,表达PU.1的细胞响应于巨噬细胞集落刺激因子(M-CSF),随后发育成成熟巨噬细胞。使用PU.1无效和未成熟PU.1拯救细胞之间的抑制性消减杂交,发现MRP-14、Dap 12和CD 53三个基因在拯救细胞中表达,但在PU.1无效细胞中不表达。此外,这些基因在M-CSF诱导的PU.1拯救细胞成熟过程中受到调节。PU.1无效和拯救的早期单核细胞提供了一个有用的模型,以研究PU.1在巨噬细胞发育中的作用。
The requirement of the transcription factor PU.1 for macrophage development has been well documented. However, the target genes regulated by PU.1 controlling macrophage maturation are not known. A granulocyte macrophage colony stimulating factor (GM-CSF)-dependent PU.1 null monocytic precursor cell was stably transduced with a PU.1-expressing retrovirus. The expression of PU.1 altered the surface expression of a few proteins expressed on monocytes; these cells, however, remained GM-CSF dependent and maintained an immature phenotype. In contrast to the PU.1 null cells, the cells expressing PU.1 responded to macrophage colony stimulating factor (M-CSF) with subsequent development into mature macrophages. Using suppressive subtractive hybridization between the PU.1 null and immature PU.1 rescued cells, three genes, MRP-14, Dap12 and CD53, were found expressed in the rescued cells, but not in the PU.1 null cells. In addition, these genes were modulated during M-CSF-induced maturation of the PU.1 rescued cells. The PU.1 null and rescued early monocytic cells provide a useful model to study the role of PU.1 in macrophage development.