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

• Main Authors: Peter J. Arthur-Farraj, Claire C. Morgan, Martyna Adamowicz, Jose A. Gomez-Sanchez, Shaline V. Fazal, Anthony Beucher, Bonnie Razzaghi, Rhona Mirsky, Kristjan R. Jessen, Timothy J. Aitman
• Format: Article
• Language: English
• Published: Elsevier 2017-09-01
• Series: Cell Reports
• Subjects: Schwann cell; repair Schwann cell; nerve injury; nerve regeneration; epigenetics; c-Jun; DNA methylation; microRNA; long non-coding RNA
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717311890

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.