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

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

Author information

1
Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK; Department of Medicine, Imperial College, London W12 0NN, UK; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. Electronic address: p.arthurfarraj@gmail.com.
2
Department of Medicine, Imperial College, London W12 0NN, UK.
3
Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH16 2XU, UK.
4
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
5
Department of Medicine, Imperial College, London W12 0NN, UK; Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH16 2XU, UK. Electronic address: tim.aitman@ed.ac.uk.

Abstract

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

PMID:
28903050
PMCID:
PMC5608958
DOI:
10.1016/j.celrep.2017.08.064
[Indexed for MEDLINE]
Free PMC Article

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