Department of Medicine, University of California, San Diego, San Diego, CA, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, CA, USA; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, San Diego, CA, USA.
Mol Cell. 2021 Oct 7;81(19):3888-3903. doi: 10.1016/j.molcel.2021.08.004. Epub 2021 Aug 30.
The development and functional potential of metazoan cells is dependent on combinatorial roles of transcriptional enhancers and promoters. Macrophages provide exceptionally powerful model systems for investigation of mechanisms underlying the activation of cell-specific enhancers that drive transitions in cell fate and cell state. Here, we review recent advances that have expanded appreciation of the diversity of macrophage phenotypes in health and disease, emphasizing studies of liver, adipose tissue, and brain macrophages as paradigms for other tissue macrophages and cell types. Studies of normal tissue-resident macrophages and macrophages associated with cirrhosis, obese adipose tissue, and neurodegenerative disease illustrate the major roles of tissue environment in remodeling enhancer landscapes to specify the development and functions of distinct macrophage phenotypes. We discuss the utility of quantitative analysis of environment-dependent changes in enhancer activity states as an approach to discovery of regulatory transcription factors and upstream signaling pathways.
后生动物细胞的发育和功能潜力取决于转录增强子和启动子的组合作用。巨噬细胞为研究驱动细胞命运和细胞状态转变的细胞特异性增强子激活的机制提供了特别强大的模型系统。在这里，我们回顾了最近的进展，这些进展扩大了对健康和疾病中巨噬细胞表型多样性的认识，强调了对肝脏、脂肪组织和大脑巨噬细胞的研究，这些研究为其他组织巨噬细胞和细胞类型提供了范例。对正常组织驻留巨噬细胞和与肝硬化、肥胖脂肪组织和神经退行性疾病相关的巨噬细胞的研究说明了组织环境在重塑增强子景观以指定不同巨噬细胞表型的发育和功能方面的主要作用。我们讨论了定量分析环境依赖性增强子活性状态变化作为发现调节转录因子和上游信号通路的方法的实用性。
