Dual Roles of Nerve-Derived Precursor Cells During Adult Mammalian Tissue Regeneration

Accumulating evidence suggests that endogenous tissue-resident precursors and stem cells play an important role in mediating the repair and regeneration of various adult tissues. Peripheral nerve innervation, found throughout all organs, is known to be an essential component of this regenerative injury response across various tissues and species, but through predominantly ill-defined mechanisms. Thus, here we utilized lineage tracing strategies combined with other approaches in order to ask how peripheral nerve-derived precursor cells might contribute towards mammalian tissue repair and regeneration. Using the adult mouse digit tip as a model to study multi-tissue regeneration, we first showed that following amputation of the distal digit, neural crest-derived Sox2-positive Schwann cells associated with nerves dedifferentiate to a precursor-like state and secrete growth factors including PDGF-AA and oncostatin M which stimulate the proliferation of surrounding mesenchymal cells. While normal regeneration was perturbed following surgical denervation or targeted genetic ablation of Sox2-positive Schwann cells, we showed that it could be largely rescued by transplantation of exogenous Schwann cells or their secreted ligands into denervated digits.Ph.D