与老年人感觉性和代谢性听力损失的遗传易感性相关的不同耳蜗细胞类型

文献信息

中文摘要

听力损失是一种异质性疾病，可分为具有不同遗传和细胞组分的不同亚型。为了研究年龄相关性听力损失（ARHL）感觉和代谢组分的遗传基础所涉及的耳蜗细胞类型，我们使用单细胞疾病相关性评分工具，将人类全基因组关联研究数据与小鼠耳蜗单细胞RNA测序数据进行了整合。这些分析显示，与ARHL感觉组分相关的基因在毛细胞中表达最高，而与ARHL代谢组分相关的基因在螺旋神经节神经元中表达最高。我们还研究了ARHL相关基因表达模式在同一细胞类型的亚群之间是否存在差异。感觉性听力损失相关基因在年轻小鼠的支持细胞亚群中表现出差异表达，而代谢性听力损失相关基因在老年小鼠血管纹的中间细胞亚群中表现出差异。这些发现为不同ARHL亚型具有不同的遗传和细胞风险特征提供了证据，提示预防和治疗策略可能需要在不同生命阶段靶向特定的细胞群体。

英文摘要

Hearing loss is a heterogeneous condition that can be classified into different subtypes with diverse genetic and cellular components. To investigate the cochlear cell types underlying the genetic basis of sensory and metabolic components of age-related hearing loss (ARHL), we integrated human genome-wide association study data with mouse cochlear single-cell RNA sequencing data using the single-cell disease relevance score tool. These analyses revealed that genes associated with the sensory component of ARHL were most highly expressed in hair cells, while genes associated with the metabolic component of ARHL were most highly expressed in spiral ganglion neurons. We also investigated whether ARHL-associated gene expression patterns differed across subpopulations of the same cell type. Sensory hearing loss-associated genes showed differential expression across supporting cell subpopulations in younger mice, whereas metabolic hearing loss-associated genes exhibited differences across intermediate cell subpopulations of the stria vascularis in older mice. These findings provide evidence for the role of distinct genetic and cellular risk profiles for different ARHL subtypes, suggesting that prevention and therapeutic strategies may require targeting specific cell populations at different life stages.