The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK.
Immunol Rev. 2014 Nov;262(1):74-84. doi: 10.1111/imr.12211.
Monocytes and macrophages differentiate from progenitor cells under the influence of colony-stimulating factors. Genome-scale data have enabled the identification of the sets of genes that are associated with specific functions and the mechanisms by which thousands of genes are regulated in response to pathogen challenge. In large datasets, it is possible to identify large sets of genes that are coregulated with the transcription factors that regulate them. They include macrophage-specific genes, interferon-responsive genes, early inflammatory genes, and those associated with endocytosis. Such analyses can also extract macrophage-associated signatures from large cancer tissue datasets. However, cluster analysis provides no support for a signature that distinguishes macrophages from antigen-presenting dendritic cells, nor the classification of macrophage activation states as classical versus alternative, or M1 versus M2. Although there has been a focus on a small subset of lineage-enriched transcription factors, such as PU.1, more than half of the transcription factors in the genome can be expressed in macrophage lineage cells under some state of activation, and they interact in a complex network. The network architecture is conserved across species, but many of the target genes evolve rapidly and differ between mouse and human. The data and publication deluge related to macrophage biology require the development of new analytical tools and ways of presenting information in an accessible form.
单核细胞和巨噬细胞在集落刺激因子的影响下从祖细胞分化而来。基因组规模的数据使我们能够确定与特定功能相关的基因集，以及成千上万的基因在应对病原体挑战时如何受到调控的机制。在大型数据集，有可能确定与调节它们的转录因子共同调控的大量基因集。它们包括巨噬细胞特异性基因、干扰素反应基因、早期炎症基因和与吞噬作用相关的基因。这种分析还可以从大型癌症组织数据集中提取与巨噬细胞相关的特征。然而，聚类分析并不能为区分巨噬细胞和抗原呈递树突状细胞的特征提供支持，也不能对巨噬细胞的激活状态进行经典与替代、M1 与 M2 的分类。虽然人们一直关注一小部分谱系特异性转录因子，如 PU.1，但在某些激活状态下，基因组中超过一半的转录因子可以在巨噬细胞谱系细胞中表达，它们在一个复杂的网络中相互作用。该网络架构在物种间是保守的，但许多靶基因在快速进化，并且在小鼠和人类之间存在差异。与巨噬细胞生物学相关的数据和出版物如潮水般涌现，这需要开发新的分析工具和以易于访问的形式呈现信息的方法。
