Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Department of Psychiatry, University of California Los Angeles, Los Angeles, CA, USA.
Nature. 2020 May;581(7806):77-82. doi: 10.1038/s41586-020-2200-5. Epub 2020 Apr 15.
Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury; however, the molecular mechanisms that underlie this regeneration are unknown. Here we perform translational profiling specifically of corticospinal tract (CST) motor neurons in mice, to identify their 'regenerative transcriptome' after spinal cord injury and NPC grafting. Notably, both injury alone and injury combined with NPC grafts elicit virtually identical early transcriptomic responses in host CST neurons. However, in mice with injury alone this regenerative transcriptome is downregulated after two weeks, whereas in NPC-grafted mice this transcriptome is sustained. The regenerative transcriptome represents a reversion to an embryonic transcriptional state of the CST neuron. The huntingtin gene (Htt) is a central hub in the regeneration transcriptome; deletion of Htt significantly attenuates regeneration, which shows that Htt has a key role in neural plasticity after injury.
脊髓源性神经祖细胞（NPC）移植物可促进皮质脊髓束（CST）轴突的强烈再生，并在脊髓损伤后恢复前肢功能；然而，这种再生的分子机制尚不清楚。在这里，我们专门对小鼠的 CST 运动神经元进行了转化谱分析，以确定它们在脊髓损伤和 NPC 移植后的“再生转录组”。值得注意的是，单独的损伤和损伤结合 NPC 移植都会在宿主 CST 神经元中引发几乎相同的早期转录组反应。然而，在单独损伤的小鼠中，这种再生转录组在两周后下调，而在 NPC 移植的小鼠中则持续存在。再生转录组代表了 CST 神经元向胚胎转录状态的逆转。亨廷顿基因（Htt）是再生转录组中的一个核心枢纽；Htt 的缺失显著减弱了再生，这表明 Htt 在损伤后的神经可塑性中起着关键作用。
