Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord.
Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord.
复制标题
少突胶质细胞前体细胞阻止感觉轴突再生为脊髓。
DOI：
10.1016/j.celrep.2023.113068
复制
发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Son,Young-Jin
中科院分区：
文献类型：
--
作者：
Kim,Hyukmin;Skuba,Andy;Xia,Jingsheng;Han,SungBaek;Zhai,Jinbin;Hu,Huijuan;Kang,ShinH;Son,Young-Jin
当初级体感轴突重新进入脊髓时，它们会停止再生，导致无法治愈的感觉丧失。是什么逮捕了他们，目前尚不清楚。我们之前表明轴突通过与未知的非神经元细胞形成突触接触而停止。在这里，我们将成年小鼠中的这些细胞鉴定为少突胶质细胞前体细胞（OPC）。我们还发现，只有少数轴突通过形成营养不良末端而停止再生，仅在中枢神经系统：周围神经系统（PNS）边界处，其中OPC不存在。大多数轴突停止与密集的 OPC 过程网络接触。实时成像、免疫电子显微镜 (immuno-EM) 和 OPC-背根神经节 (DRG) 共培养还表明，轴突通过与 OPC 形成突触而快速固定。基因 OPC 消融使许多轴突能够继续再生到脊髓深处。我们提出感觉轴突通过遇到诱导突触前分化的 OPC 来停止再生。我们的研究结果表明，OPCs 是一种主要的再生屏障，可防止脊髓根损伤后感觉回路的椎内恢复。
Primary somatosensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:peripheral nervous system (PNS) borderline where OPCs are absent. Most axons stop in contact with a dense network of OPC processes. Live imaging, immuno-electron microscopy (immuno-EM), and OPC-dorsal root ganglia (DRG) co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.