Abstract
Cells of the monocyte/macrophage lineage (MFs) are an essential component of the body’s innate ability to restore tissue function after injury. Yet, the molecular signals required to coordinate the transition from pro-inflammatory clearance of injury-associated MFs to pro-resolution signals that rebuild tissue architecture and restore homeostasis remain unresolved. Here we decipher whether metabolic reprogramming drives MF activation and function in healing tissues. By combining multiple methods including generation of genetically modified mouse models, bulk and single cell transcriptomic analysis of wound MFs at different stages and functional metabolic analysis, we demonstrate that skin injury induces distinct metabolic programs in wound MFs, which drive stage specific and critical repair functions over the time course of healing.
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