Peripheral glia constitute a pro-reparative niche triggering skin wound healing [Spatial Transcriptomics]
Skin repair is a complex, dynamic process involving multiple cell types. Using multiplex imaging, spatial transcriptomics, and single-cell RNA sequencing, we show that peripheral nerves —containing repair glia— form a pro-reparative niche closely interacting with macrophages and proliferating fibroblasts in acute skin wounds. Repair glia function as critical early-stage regulators of wound healing by initiating the inflammatory response throughsecretion of monocyte chemoattractant proteins, such as CCL2, which recruit monocyte derived macrophages. Accordingly, depletion of repair glia as well as glia-specific deletion of CCL2 reduces the number of macrophages, leading to impaired fibroblast proliferation and diminished fibroblast to myofibroblast transition. These findings position repair glia as a central component of the pro-reparative niche, coordinating the early immune response and orchestrating the temporal progression of wound healing. Overall design: spatial transcriptomics profiling of two regenerating skin wounds of Plp1-CreERT2:tdTomato control mouse at 4 days follwing injury.