Journal
MOLECULAR CELL
Volume 81, Issue 19, Pages 3888-3903Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2021.08.004
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Funding
- NIH [NS096170, AG056511, DK091183, HL147835]
- Leducq Transatlantic Network grant [16CVD01]
- NSF
- [T32 5T32GM008806-20]
- [P30 DK063491]
- [T32 DK007044]
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This review highlights recent advances in understanding the diversity of macrophage phenotypes in health and disease, with a focus on studying liver, adipose tissue, and brain macrophages as paradigms for other tissue macrophages and cell types.
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.
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