Mesenchymal precursor cells in adult nerves contribute to mammalian tissue repair and regeneration

Peripheral innervation plays an important role in regulating tissue repair and regeneration. Here, we provide evidence that injured peripheral nerves provide a reservoir of mesenchymal precursor cells that can directly contribute to murine digit tip regeneration and skin repair. In particular, using single-cell RNA sequencing and lineage tracing we identify transcriptionally-distinct mesenchymal cell populations within the control and injured adult nerve, including neural crest-derived cells in the endoneurium with characteristics of mesenchymal precursor cells. Culture and transplantation studies show that these nerve-derived mesenchymal cells have the potential to differentiate into non-nerve lineages. Moreover, following digit tip amputation, the neural crest-derived nerve mesenchymal cells contribute to the regenerative blastema and ultimately to the regenerated bone. Similarly, neural crest derived nerve mesenchymal cells contribute to the dermis during skin wound healing. These findings support a model where peripheral nerves directly contribute mesenchymal precursor cells to promote repair and regeneration of injured mammalian tissues.