Abstract
SummaryRepair 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.
Highlights
Schwann cells in the peripheral nervous system (PNS) play a crucial role in the repair of injured nerves (Jessen and Mirsky, 2016)
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
Summary
Schwann cells in the peripheral nervous system (PNS) play a crucial role in the repair of injured nerves (Jessen and Mirsky, 2016). The myelin and non-myelin (Remak) Schwann cells that normally ensheath undamaged axons undergo extensive molecular and cellular changes to generate a distinct Schwann cell phenotype, the repair Schwann cell. This cell is specialized for maintaining survival of injured neurons, supports axonal regeneration, and is essential for functional nerve repair. Formation of repair Schwann cells requires the downregulation of genes involved in myelination and upregulation of an injury-specific program of gene expression (Arthur-Farraj et al, 2012; Fontana et al, 2012; Jessen and Mirsky, 2016). Repair Schwann cell formation is regulated by the AP-1 transcription factor (TF) C-JUN; several other factors have subsequently been shown to regulate the Schwann cell response to nerve injury (Arthur-Farraj et al, 2012; reviewed in Boerboom et al, 2017)
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