Changes in the Coding and Non-coding Transcriptome and DNA Methylome that Define the Schwann Cell Repair Phenotype after Nerve Injury

Cell Rep. 2017 Sep 12;20(11):2719-2734. doi: 10.1016/j.celrep.2017.08.064.


Repair Schwann cells play a critical role in orchestrating nerve repair after injury, but the cellular and molecular processes that generate them are poorly understood. Here, we perform a combined whole-genome, coding and non-coding RNA and CpG methylation study following nerve injury. We show that genes involved in the epithelial-mesenchymal transition are enriched in repair cells, and we identify several long non-coding RNAs in Schwann cells. We demonstrate that the AP-1 transcription factor C-JUN regulates the expression of certain micro RNAs in repair Schwann cells, in particular miR-21 and miR-34. Surprisingly, unlike during development, changes in CpG methylation are limited in injury, restricted to specific locations, such as enhancer regions of Schwann cell-specific genes (e.g., Nedd4l), and close to local enrichment of AP-1 motifs. These genetic and epigenomic changes broaden our mechanistic understanding of the formation of repair Schwann cell during peripheral nervous system tissue repair.

Keywords: DNA methylation; Schwann cell; c-Jun; epigenetics; long non-coding RNA; microRNA; nerve injury; nerve regeneration; repair Schwann cell.

MeSH terms

  • Animals
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Enhancer Elements, Genetic / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Nerve Regeneration / genetics*
  • Peripheral Nerve Injuries / genetics*
  • Peripheral Nerve Injuries / pathology
  • Phenotype
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Schwann Cells / pathology*
  • Sequence Analysis, RNA
  • Transcription Factor AP-1 / metabolism
  • Transcriptome / genetics*


  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factor AP-1