Mesenchymal Precursor Cells in Adult Nerves Contribute to Mammalian Tissue Repair and Regeneration

Cell Stem Cell. 2019 Feb 7;24(2):240-256.e9. doi: 10.1016/j.stem.2018.10.024. Epub 2018 Nov 29.

Abstract

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, 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.

Keywords: bone repair; digit tip regeneration; mesenchymal precursor cells; neural crest; peripheral nerve; single-cell RNA sequencing; skin wound healing; tissue regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Regeneration
  • Cell Differentiation
  • Cell Lineage
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Nerve Regeneration / physiology*
  • Nerve Tissue / pathology*
  • Neural Crest / cytology
  • Osteogenesis
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Schwann Cells / pathology
  • Sciatic Nerve / injuries
  • Sciatic Nerve / pathology
  • Transcription, Genetic
  • Transcriptome / genetics
  • Wound Healing*

Substances

  • Receptor, Platelet-Derived Growth Factor alpha

Grant support