Satellite glial cells promote regenerative growth in sensory neurons.

Satellite glial cells promote regenerative growth in sensory neurons.
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卫星胶质细胞促进感觉神经元的再生生长。

DOI:
10.1038/s41467-020-18642-y
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发表时间:
2020-09-29
影响因子:
16.6
通讯作者:
Cavalli V
Cavalli V
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Avraham O;Deng PY;Jones S;Kuruvilla R;Semenkovich CF;Klyachko VA;Cavalli V

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外周感觉神经元在神经损伤后再生其轴突以使功能恢复。已知感觉神经元中的内在机制调节神经修复,但是完全包裹神经元索马体的卫星胶质细胞(SGC)是否有助于神经再生仍然未被探索。使用单细胞RNAseq方法,我们揭示了SGC与许旺细胞不同,与星形胶质细胞有相似之处。神经损伤引起与脂肪酸合成和过氧化物酶体增殖物激活受体(PPARα)信号转导相关的基因表达的变化。SGC中脂肪酸合酶(Fasn)的条件性缺失损害轴突再生。PPARα激动剂非诺贝特挽救了SGC中缺乏Fasn的小鼠中受损的轴突再生。这些结果表明,在SGC中FXR下游的PPARα活性有助于促进成人周围神经中的轴突再生,并强调感觉神经元及其周围的胶质细胞被形成协调神经修复的功能单元。卫星神经胶质细胞对周围神经再生的作用尚不清楚。在这里,作者表明,卫星胶质细胞在转录上与雪旺细胞不同,与星形胶质细胞有相似之处,并且在损伤后,它们通过Fasn-PPARα信号通路促进轴突再生。
Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase (Fasn) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair. The contribution of satellite glia to peripheral nerve regeneration is unclear. Here, the authors show that satellite glia are transcriptionally distinct from Schwann cells, share similarities with astrocytes, and, upon injury, they contribute to axon regeneration via Fasn-PPARα signalling pathway.
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