Adult DRG: Identification of a sacral, visceral sensory transcriptome in embryonic and adult mice

Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially lead to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively somatic sensory neurons. This was performed in male and female mice (adult and E18.5). By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal level. We identified many novel genes not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways. Comparison of dorsal root ganglia from lumbar and sacral spine regions in adult C57Bl6 mice内脏感觉神经元（visceral sensory neurons）可编码健康器官的特异性感觉，并引发对普通镇痛药耐受的疼痛状态。转录组分析（transcriptome analysis）正重塑我们对感觉神经元亚型的认知，但现有研究多聚焦于躯体感觉神经元（somatic sensory neurons），或是以内脏神经元占少数的总神经元群体。本研究旨在明确骶部内脏感觉神经元特异性表达的转录本，以此为基础解析这类神经元的独特生物学特性，并有望为盆腔内脏痛（pelvic visceral pain）鉴定全新的镇痛靶点。我们的研究策略为：对比包含躯体神经元与骶部内脏神经元的骶段背根神经节（dorsal root ganglia, DRG），与仅含躯体感觉神经元的邻近腰段背根神经节之间的差异表达基因。实验对象涵盖成年及胚胎期E18.5的雌雄小鼠。通过开发一种将分析限定于伤害性感受Trpv1神经元的方法，我们在脊髓节段间检测到了更多的差异表达基因。本研究鉴定出诸多此前未被报道与盆腔内脏感觉或伤害性感受相关的全新基因。感觉神经节的整体转录组中仅检测到有限的性别差异，但在骶段尤其是Trpv1伤害性感受神经元中，性别差异更为显著。本数据集将助力开发调控成熟及发育中感觉神经元与伤害性感受通路的全新工具。成年C57BL/6小鼠腰段与骶段脊柱来源背根神经节的对比分析