Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: New molecules and patterns of gene expression
Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: New molecules and patterns of gene expression
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DOI：
10.4049/jimmunol.177.10.7303
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Mantovani, Alberto
中科院分区：
文献类型：
--
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
对与人单核细胞向巨噬细胞分化和向M1或M2表型极化相关的基因表达谱的综合分析导致以下主要结果：1）M-CSF驱动的单核细胞向巨噬细胞分化与细胞周期基因的激活相关，证实了单核细胞的增殖潜力被低估。2)M-CSF导致M2转录组的大部分表达，表明在稳态条件下发生向M2的默认转变。3)参与代谢活动的基因的调节是巨噬细胞分化和极化的显著特征。4)脂质代谢是调节转录物的主要类别，在M1细胞中具有预期的环加氧酶2上调，在M2细胞中具有意外的环加氧酶1上调。5)每一步的特点是不同的剧目的G蛋白偶联受体，5个核苷酸受体作为新的M2相关基因。6)极化巨噬细胞的趋化因子组是深刻的多样性和新的差异表达的趋化因子的报告。因此，转录组分析揭示了与人单核细胞至巨噬细胞分化和极化激活相关的新分子和特征，其可能代表病理生理学中的候选靶标。
Comprehensive analysis of the gene expression profiles associated with human monocyte-to-macrophage differentiation and polarization toward M1 or M2 phenotypes led to the following main results: 1) M-CSF-driven monocyte-to-macrophage differentiation is associated with activation of cell cycle genes, substantiating the underestimated proliferation potential of monocytes. 2) M-CSF leads to expression of a substantial part of the M2 transcriptome, suggesting that under homeostatic conditions a default shift toward M2 occurs. 3) Modulation of genes involved in metabolic activities is a prominent feature of macrophage differentiation and polarization. 4) Lipid metabolism is a main category of modulated transcripts, with expected up-regulation of cyclo-oxygenase 2 in M1 cells and unexpected cyclo-oxygenase 1 up-regulation in M2 cells. 5) Each step is characterized by a different repertoire of G protein-coupled receptors, with five nucleotide receptors as novel M2-associated genes. 6) The chemokinome of polarized macrophages is profoundly diverse and new differentially expressed chemokines are reported. Thus, transcriptome profiling reveals novel molecules and signatures associated with human monocyte-to-macrophage differentiation and polarized activation which may represent candidate targets in pathophysiology.