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.
Department of Medicine, Imperial College, London W12 0NN, UK.
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.
修复 Schwann 细胞在损伤后协调神经修复中起着关键作用，但它们产生的细胞和分子过程还知之甚少。在这里，我们在神经损伤后进行了全基因组、编码和非编码 RNA 以及 CpG 甲基化的联合研究。我们表明，参与上皮-间充质转化的基因在修复细胞中富集，并且我们在 Schwann 细胞中鉴定了几种长非编码 RNA。我们证明，AP-1 转录因子 C-JUN 调节修复 Schwann 细胞中某些 microRNA 的表达，特别是 miR-21 和 miR-34。令人惊讶的是，与发育过程不同，CpG 甲基化的变化在损伤中受到限制，仅限于特定位置，例如 Schwann 细胞特异性基因（例如 Nedd4l）的增强子区域，并且靠近 AP-1 基序的局部富集。这些遗传和表观遗传变化拓宽了我们对周围神经系统组织修复过程中修复 Schwann 细胞形成的机制理解。
