Satellite Glial Cells Give Rise to Nociceptive Sensory Neurons
Satellite Glial Cells Give Rise to Nociceptive Sensory Neurons
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卫星胶质细胞产生伤害性感觉神经元
DOI：
10.1007/s12015-020-10102-w
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发表时间：
2021-01-03
影响因子：
4.8
通讯作者：
Zhang, Huanxiang
中科院分区：
文献类型：
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作者：
Wang, Dongyan;Lu, Junhou;Zhang, Huanxiang
背根神经节（DRG）感觉神经元能通过脊髓将伤害性刺激的信息传递到大脑皮层，在痛觉通路中起重要作用。疼痛通路的改变导致CIPA（先天性疼痛不敏感伴无汗症）或慢性疼痛。越来越多的证据表明，神经损伤导致背根节神经元再生，这可能有助于反馈性疼痛调制。因此，探讨DRG神经元的再生过程将为持续性病理性刺激提供新的认识，并有助于重塑躯体感觉功能。有研究表明，卫星胶质细胞（satellite glial cells，SGCs）的一个亚群表达Nestin和p75，并可分化为神经胶质细胞和神经元，提示SGCs可能具有分化可塑性。我们的研究结果表明，DRG衍生的SGCs（DRG SGCs）高度表达神经嵴细胞标志物Nestin，Sox 2，Sox 10和p75，并在组蛋白去乙酰化酶抑制剂VPA，Wnt通路激活剂CHIR 99021，Notch通路抑制剂RO 4929097和FGF通路抑制剂SU 5402的存在下分化为伤害性感觉神经元。伤害性感觉神经元表达多种功能相关基因（SCN 9A、SCN 10A、SP、Trpv 1和TrpA 1），并能够产生动作电位和电压门控Na+电流。此外，我们发现，这些细胞表现出快速的钙瞬变响应辣椒素通过结合到Trpv 1香草素受体，证实了DRG-SGC衍生的细胞是伤害性感觉神经元。此外，我们发现Wnt信号通过调节特异性转录因子Runx 1的表达促进DRG-SGCs分化为伤害性感觉神经元，而Notch和FGF信号通路参与了SCN 9A的表达。这些结果表明DRG-SGCs具有干细胞特征，可以有效分化为功能性伤害性感觉神经元，为感觉神经元相关疾病的临床治疗提供了线索。图形摘要
Dorsal root ganglia (DRG) sensory neurons can transmit information about noxious stimulus to cerebral cortex via spinal cord, and play an important role in the pain pathway. Alterations of the pain pathway lead to CIPA (congenital insensitivity to pain with anhidrosis) or chronic pain. Accumulating evidence demonstrates that nerve damage leads to the regeneration of neurons in DRG, which may contribute to pain modulation in feedback. Therefore, exploring the regeneration process of DRG neurons would provide a new understanding to the persistent pathological stimulation and contribute to reshape the somatosensory function. It has been reported that a subpopulation of satellite glial cells (SGCs) express Nestin and p75, and could differentiate into glial cells and neurons, suggesting that SGCs may have differentiation plasticity. Our results in the present study show that DRG-derived SGCs (DRG-SGCs) highly express neural crest cell markers Nestin, Sox2, Sox10, and p75, and differentiate into nociceptive sensory neurons in the presence of histone deacetylase inhibitor VPA, Wnt pathway activator CHIR99021, Notch pathway inhibitor RO4929097, and FGF pathway inhibitor SU5402. The nociceptive sensory neurons express multiple functionally-related genes (SCN9A, SCN10A, SP, Trpv1, and TrpA1) and are able to generate action potentials and voltage-gated Na+currents. Moreover, we found that these cells exhibited rapid calcium transients in response to capsaicin through binding to the Trpv1 vanilloid receptor, confirming that the DRG-SGC-derived cells are nociceptive sensory neurons. Further, we show that Wnt signaling promotes the differentiation of DRG-SGCs into nociceptive sensory neurons by regulating the expression of specific transcription factor Runx1, while Notch and FGF signaling pathways are involved in the expression of SCN9A. These results demonstrate that DRG-SGCs have stem cell characteristics and can efficiently differentiate into functional nociceptive sensory neurons, shedding light on the clinical treatment of sensory neuron-related diseases.Graphical Abstract