Lopes Douglas M, Denk Franziska, McMahon Stephen B
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
Front Mol Neurosci. 2017 Sep 26;10:304. doi: 10.3389/fnmol.2017.00304. eCollection 2017.
The dorsal root ganglia (DRG) and trigeminal ganglia (TG) are clusters of cell bodies of highly specialized sensory neurons which are responsible for relaying information about our environment to the central nervous system. Despite previous efforts to characterize sensory neurons at the molecular level, it is still unknown whether those present in DRG and TG have distinct expression profiles and therefore a unique molecular fingerprint. To address this question, we isolated lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin-GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses showed that, despite being overwhelmingly similar, a number of genes are differentially expressed in DRG and TG neurons. Importantly, we identified 24 genes which were uniquely expressed in either ganglia, including an arginine vasopressin receptor and several homeobox genes, giving each population a distinct molecular fingerprint. We compared our findings with published studies to reveal that many genes previously reported to be present in neurons are in fact likely to originate from other cell types in the ganglia. Additionally, our neuron-specific results aligned well with a dataset examining whole human TG and DRG. We propose that the data can both improve our understanding of primary afferent biology and help contribute to the development of drug treatments and gene therapies which seek targets with unique or restricted expression patterns.
背根神经节(DRG)和三叉神经节(TG)是高度特化的感觉神经元的细胞体簇,负责将有关我们周围环境的信息传递到中枢神经系统。尽管之前已努力在分子水平上对感觉神经元进行表征,但DRG和TG中的神经元是否具有不同的表达谱,进而具有独特的分子指纹,仍然未知。为了解决这个问题,我们使用荧光激活细胞分选技术从Advillin-GFP转基因小鼠中分离出腰段DRG和TG神经元,并进行了RNA测序。我们的转录组分析表明,尽管DRG和TG神经元绝大多数相似,但仍有许多基因在二者中差异表达。重要的是,我们鉴定出24个在任一神经节中独特表达的基因,包括一个精氨酸加压素受体和几个同源框基因,这赋予了每个群体独特的分子指纹。我们将我们的研究结果与已发表的研究进行比较,以揭示许多先前报道存在于神经元中的基因实际上可能起源于神经节中的其他细胞类型。此外,我们神经元特异性的结果与一项检查整个人类TG和DRG的数据集高度吻合。我们认为,这些数据既能增进我们对初级传入生物学的理解,又有助于推动寻求具有独特或受限表达模式靶点的药物治疗和基因治疗的发展。