Molecular signatures of mouse TRPV1-lineage neurons revealed by RNA-Seq transcriptome analysis.
Molecular signatures of mouse TRPV1-lineage neurons revealed by RNA-Seq transcriptome analysis.
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DOI：
10.1016/j.jpain.2014.09.010
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发表时间：
2014-12
期刊：
影响因子：
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通讯作者：
Iadarola MJ
中科院分区：
文献类型：
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作者：
Goswami SC;Mishra SK;Maric D;Kaszas K;Gonnella GL;Clokie SJ;Kominsky HD;Gross JR;Keller JM;Mannes AJ;Hoon MA;Iadarola MJ
疼痛神经系统的疾病通常是慢性的，如果治疗无效，会严重降低生活质量。疼痛通路始于背根或三叉神经节中的感觉神经元，并且表达TRPV 1离子通道的神经元亚群传递疼痛热和炎症的感觉，并且在由癌症和关节炎引起的临床疼痛中发挥基本作用。在本研究中，我们通过下一代深度RNA-Seq、遗传神经元标记与荧光激活细胞分选或神经元选择性化学消融的联合应用，阐明了感觉神经节中TRPV 1谱系神经元和非TRPV 1神经胶质细胞群体的完整转录组。RNA-Seq精确地定量基因表达，这是用大多数其他方法难以确定的参数，特别是对于非常低和非常高表达的基因。差异表达的基因存在于从细胞核到质膜的细胞功能的每个水平。我们在TRPV 1中发现了许多配体受体对，这表明自主突触前调节可能是伤害性神经元的主要调节机制。这些数据以定量的细胞群体特异性方式定义了一组独特的和临床上重要的疼痛感受神经元的分子特征，并为理解TRPV 1伤害性神经元的转录组提供了一个总体框架。
Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia and the neuronal subpopulations that express the TRPV1 ion channel transduce sensations of painful heat and inflammation, and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuro-glial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population suggesting that autonomous presynaptic regulation maybe a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons.