长读长RNA测序绘制过敏性鼻炎小鼠模型中三叉神经节的异构体图谱

文献信息

中文摘要

背景： 三叉神经节（TG）在过敏性鼻炎（AR）中发挥关键作用，通过感觉神经元激活介导鼻痒和打喷嚏等症状。然而，其潜在的转录组机制仍不清楚。短读长RNA测序难以准确捕获复杂的转录本异构体，而长读长测序提供全长覆盖但定量能力有限。在此，我们结合两种技术全面描绘AR小鼠模型中的TG转录组。
结果： 我们从13,011个已知基因和237个新基因中鉴定出25,988个高置信度全长异构体，其中包括7,543个（29.02%）参考数据库中不存在的新异构体。这些异构体富集于RNA剪接和加工基因中。可变第一外显子是最常见的剪接事件，且在新异构体中尤为频繁。AR诱导基因表达、剪接动态和启动子活性的变化，提示神经-免疫串扰。单细胞RNA测序整合进一步揭示，虽然一些基因缺乏细胞类型特异性表达，但其可变剪接模式具有高度细胞类型特异性，提示可变剪接可能在使基因功能在不同细胞类型间多样化方面发挥关键作用。
结论： 这些发现提供了一个全面的全长转录组数据集，有助于深入探索三叉神经节中感觉改变与AR之间的相互作用。

英文摘要

BACKGROUND: The trigeminal ganglion (TG) plays a key role in allergic rhinitis (AR), mediating symptoms like nasal itching and sneezing via sensory neuron activation. Yet, the underlying transcriptomic mechanisms remain unclear. While short-read RNA-seq struggles to accurately capture complex transcript isoforms, long-read sequencing offers full-length coverage but limited quantitation. Here, we combine both technologies to comprehensively profile the TG transcriptome in an AR mouse model.
RESULTS: We identify 25,988 high-confidence full-length isoforms from 13,011 known and 237 novel genes, including 7,543 (29.02%) novel isoforms absent from reference databases. These are enriched in RNA splicing and processing genes. Alternative first exons are the most common splicing event and are especially frequent among novel isoforms. AR induces shifts in gene expression, splicing dynamics, and promoter activity, suggesting neuro-immune crosstalk. Single-cell RNA-seq integration further reveals that while some genes lack cell type-specific expression, their alternative splicing patterns are highly cell type-specific, suggesting that AS may play a crucial role in diversifying gene function across different cell types.
CONCLUSIONS: The findings provide a comprehensive full-length transcriptome dataset, facilitating in-depth exploration of the interplay between sensory alterations and AR in trigeminal ganglion.