Transcriptional diversity during monocyte to macrophage differentiation
Transcriptional diversity during monocyte to macrophage differentiation
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DOI：
10.1016/j.imlet.2007.12.012
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Pope, Richard M.
中科院分区：
文献类型：
--
作者：
Liu, Hongtao;Shi, Bo;Pope, Richard M.
从外周血募集到组织中的单核细胞分化为巨噬细胞，这在许多疾病的发病机制中至关重要。关于单核细胞向巨噬细胞分化过程中基因表达的整体变化，以及变化模式如何识别巨噬细胞分化或功能的机制，数据有限。采用微阵列技术，我们检查了原代人单核细胞体外粘附诱导分化为巨噬细胞的转录谱。我们发现促进巨噬细胞功能的基因显着上调，包括调节免疫和防御的基因；脂质、脂肪酸和类固醇代谢；细胞粘附、碳水化合物代谢；氨基酸代谢和内吞作用。相反，绝大多数受影响的转录因子在单核细胞向巨噬细胞分化过程中下调，这表明转录抑制对于从单核细胞向巨噬细胞的转变可能很重要。然而，有限数量的转录因子被上调，其中包括C/EBP α，它可能通过调节下游基因来促进分化，这是分化的巨噬细胞的特征。这些观察结果表明，检查患者单核细胞和巨噬细胞的转录谱可以确定巨噬细胞介导的疾病的相关治疗靶点。 (C) 2007 Elsevier B.V. 保留所有权利。
Monocytes recruited into tissues from peripheral blood differentiate into macrophages, which are critical in the pathogenesis of many diseases. There is limited data concerning the global changes in the expression of genes during monocyte to macrophage differentiation, and how the patterns of change identify the mechanism contributing to macrophage differentiation or function. Employing microarray technology, we examined the transcriptional profile of in vitro adherence-induced differentiation of primary human monocytes into macrophages. We found the significant up regulation of genes contributing to the functions of macrophages, including those regulating to immunity and defense; lipid, fatty acid and steroid metabolism; cell adhesion, carbohydrate metabolism; amino acid metabolism and endocytosis. In contrast, the vast majority of transcription factors affected were down regulated during monocyte to macrophage differentiation, suggesting that transcriptional repression may be important for the transition from monocytes to macrophages. However, a limited number of transcription factors were up regulated, among these was C/EBP alpha, which may contribute to differentiation by regulating down stream genes, which are a characteristic of differentiated macrophages. These observations suggest that examination of the transcriptional profile in monocytes and macrophages in patients may identify relevant therapeutic targets in diseases mediated by macrophages. (C) 2007 Elsevier B.V. All rights reserved.