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

Peter J. Arthur-Farraj

2017

Scholarcy highlights

  • Schwann cells in the peripheral nervous system play a crucial role in the repair of injured nerves
  • Unlike during development, changes in CpG methylation are limited in injury, restricted to specific locations, such as enhancer regions of Schwann cell-specific genes, and close to local enrichment of AP-1 motifs
  • In order to investigate cell-specific coding and non-coding RNA expression and CpG methylation changes, we performed qPCR and Sanger sequencing on cultured purified Schwann cells, nerve-derived fibroblasts, and bone-marrowderived macrophages activated with lipopolysaccharide
  • The aims of the present study were to characterize more fully the genetic and epigenetic signature of the repair Schwann cell, define further how the phenotype of this cell depends on c-Jun, and determine the DNA methylation changes that accompany the conversion of myelin and Remak Schwann cells to repair Schwann cells in injured nerves
  • Using a database of all mRNAs and miRNAs currently known to have a role in epithelial-mesenchymal transition, we have shown that these genes are markedly enriched in our datasets from injured nerve samples from both wild-type and Schwann cell-specific c-Jun-knockout mice
  • When we looked in detail at one gene, Nedd4l, which is highly expressed in cultured Schwann cells, we found that there were two specific hypomethylated CpG clusters located within introns
  • These genetic and epigenomic changes broaden our mechanistic understanding of the formation of repair Schwann cell during peripheral nervous system tissue repair

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