Diversity amongst trigeminal neurons revealed by high throughput single cell sequencing

The trigeminal ganglion contains somatosensory neurons that detect a range of thermal, mechanical and chemical cues and innervate unique sensory compartments in the head and neck including the eyes, nose, mouth, meninges and vibrissae. We used single-cell sequencing and in situ hybridization to examine the cellular diversity of the trigeminal ganglion in mice, defining thirteen clusters of neurons. We show that clusters are well conserved in dorsal root ganglia suggesting they represent distinct functional classes of somatosensory neurons and not specialization associated with their sensory targets. Notably, functionally important genes (e.g. the mechanosensory channel Piezo2 and the capsaicin gated ion channel Trpv1) segregate into multiple clusters and often are expressed in subsets of cells within a cluster. Therefore, the 13 genetically-defined classes are likely to be physiologically heterogeneous rather than highly parallel (i.e., redundant) lines of sensory input. Our analysis harnesses the power of single-cell sequencing to provide a unique platform for in silico expression profiling that complements other approaches linking gene-expression with function and exposes unexpected diversity in the somatosensory system.

三叉神经节（trigeminal ganglion）包含躯体感觉神经元（somatosensory neurons），这类神经元可感知温度、机械及化学等多种刺激，并支配头颈部的特定感觉区域，包括眼、鼻、口、脑膜及触须。本研究采用单细胞测序（single-cell sequencing）与原位杂交（in situ hybridization）技术，对小鼠三叉神经节的细胞多样性开展分析，成功鉴定出13个神经元簇。研究发现，这些神经元簇在背根神经节（dorsal root ganglia）中同样保守存在，这表明它们代表了躯体感觉神经元的不同功能类别，而非由其支配的感觉靶区所介导的特化群体。值得注意的是，部分功能关键基因（例如机械敏感离子通道Piezo2与辣椒素门控离子通道Trpv1）并非局限于单一神经元簇，而是分布于多个簇中，且通常仅在单个簇内的部分细胞亚群中表达。因此，这13个由遗传特征定义的神经元类别大概率存在生理异质性，而非功能高度冗余的平行感觉传入通路。本研究借助单细胞测序的技术优势，搭建了一个独特的计算机模拟表达谱分析平台，该平台可辅助其他将基因表达与功能进行关联的研究方法，并揭示了躯体感觉系统中此前未被发现的细胞多样性。