Adipose tissue macrophage heterogeneity in the single-cell genomics era

초록

It is now well-accepted that obesity-induced inflammation plays an important role in the development of insulin resistanceand type 2 diabetes. A key source of the inflammation is the murine epididymal and human visceral adipose tissue. Thecurrent paradigm is that obesity activates multiple proinflammatory immune cell types in adipose tissue, including adi pose-tissue macrophages (ATMs), T Helper 1 (Th1) T cells, and natural killer (NK) cells, while concomitantly suppressinganti-inflammatory immune cells such as T Helper 2 (Th2) T cells and regulatory T cells (Tregs). A key feature of the currentparadigm is that obesity induces the anti-inflammatory M2 ATMs in lean adipose tissue to polarize into proinflammatory M1ATMs. However, recent single-cell transcriptomics studies suggest that the story is much more complex. Here we describethe single-cell genomics technologies that have been developed recently and the emerging results from studies usingthese technologies. While further studies are needed, it is clear that ATMs are highly heterogeneous. Moreover, while avariety of ATM clusters with quite distinct features have been found to be expanded by obesity, none truly resembleclassical M1 ATMs. It is likely that single-cell transcriptomics technology will further revolutionize the field, thereby pro moting our understanding of ATMs, adipose-tissue inflammation, and insulin resistance and accelerating the developmentof therapies for type 2 diabetes.

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