Stereotyped transcriptomic transformation of somatosensory neurons in response to injury
Stereotyped transcriptomic transformation of somatosensory neurons in response to injury
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DOI：
10.7554/elife.49679
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发表时间：
2019-10-08
期刊：
影响因子：
7.7
通讯作者：
Ryba, Nicholas
中科院分区：
文献类型：
--
作者：
Nguyen, Minh Q.;Le Pichon, Claire E.;Ryba, Nicholas
在小鼠身上，幸存的神经损伤复制了人类神经病理性疼痛的症状，并诱导了体感神经元中许多基因的上调。在这里，我们使用单细胞转录本在细胞水平上探讨三叉神经眶下部分横断术的影响。未损伤的神经元不受主要神经分支横断的影响，分为许多不同的类别。与之形成鲜明对比的是，轴突切断术迅速将受损神经元转变为两个新的、密切相关的类别，几乎所有原始身份都丢失了。值得注意的是，感觉神经元在各种轻微的外周损伤后也采用了这种转录状态。通过对受损神经元进行基因标记，我们证明了损伤诱导的转化是可逆的，受损细胞慢慢恢复正常的基因表达谱。因此，我们的数据揭示了转录可塑性，以前被认为是慢性疼痛的驱动因素，是对许多类型的损伤的程序化反应，以及在伤口愈合过程中调节感觉的潜在机制。
In mice, spared nerve injury replicates symptoms of human neuropathic pain and induces upregulation of many genes in somatosensory neurons. Here we used single cell transcriptomics to probe the effects of partial infraorbital transection of the trigeminal nerve at the cellular level. Uninjured neurons were unaffected by transection of major nerve branches, segregating into many different classes. In marked contrast, axotomy rapidly transformed damaged neurons into just two new and closely-related classes where almost all original identity was lost. Remarkably, sensory neurons also adopted this transcriptomic state following various minor peripheral injuries. By genetically marking injured neurons, we showed that the injury-induced transformation was reversible, with damaged cells slowly reacquiring normal gene expression profiles. Thus, our data expose transcriptomic plasticity, previously thought of as a driver of chronic pain, as a programed response to many types of injury and a potential mechanism for regulating sensation during wound healing.