Arambula Alexandra M, Gu Shoujun, Warnecke Athanasia, Schmitt Heike A, Staecker Hinrich, Hoa Michael
Department of Otolaryngology-Head & Neck Surgery, University of Kansas Medical Center, Kansas City, KS.
Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, Bethesda, MD.
Otol Neurotol Open. 2023 Mar 9;3(1):e027. doi: 10.1097/ONO.0000000000000027. eCollection 2023 Mar.
Proteins enriched in the perilymph proteome of Meńier̀e disease (MD) patients may identify affected cell types. Utilizing single-cell transcriptome datasets from the mammalian cochlea, we hypothesize that these enriched perilymph proteins can be localized to specific cochlear cell types.
The limited understanding of human inner ear pathologies and their associated biomolecular variations hinder efforts to develop disease-specific diagnostics and therapeutics. Perilymph sampling and analysis is now enabling further characterization of the cochlear microenvironment. Recently, enriched inner ear protein expression has been demonstrated in patients with MD compared to patients with other inner ear diseases. Localizing expression of these proteins to cochlear cell types can further our knowledge of potential disease pathways and subsequent development of targeted therapeutics.
We compiled previously published data regarding differential perilymph proteome profiles amongst patients with MD, otosclerosis, enlarged vestibular aqueduct, sudden hearing loss, and hearing loss of undefined etiology (controls). Enriched proteins in MD were cross-referenced against published single-cell/single-nucleus RNA-sequencing datasets to localize gene expression to specific cochlear cell types.
In silico analysis of single-cell transcriptomic datasets demonstrates enrichment of a unique group of perilymph proteins associated with MD in a variety of intracochlear cells, and some exogeneous hematologic and immune effector cells. This suggests that these cell types may play an important role in the pathology associated with late MD, suggesting potential future areas of investigation for MD pathophysiology and treatment.
Perilymph proteins enriched in MD are expressed by specific cochlear cell types based on in silico localization, potentially facilitating development of disease-specific diagnostic markers and therapeutics.
梅尼埃病（MD）患者外淋巴蛋白质组中富集的蛋白质可能有助于识别受影响的细胞类型。利用哺乳动物耳蜗的单细胞转录组数据集，我们推测这些富集的外淋巴蛋白质可以定位到特定的耳蜗细胞类型。
对人类内耳疾病及其相关生物分子变异的了解有限，阻碍了开发疾病特异性诊断和治疗方法的努力。外淋巴采样和分析现在能够进一步表征耳蜗微环境。最近，与其他内耳疾病患者相比，MD患者的内耳蛋白质表达已得到证实。将这些蛋白质的表达定位到耳蜗细胞类型可以加深我们对潜在疾病途径的了解，并有助于后续开发靶向治疗方法。
我们汇总了先前发表的关于MD、耳硬化症、前庭导水管扩大、突发性听力损失和病因不明的听力损失（对照组）患者外淋巴蛋白质组差异谱的数据。将MD中富集的蛋白质与已发表的单细胞/单核RNA测序数据集进行交叉参考，以将基因表达定位到特定的耳蜗细胞类型。
对单细胞转录组数据集的计算机分析表明，与MD相关的一组独特的外淋巴蛋白质在多种耳蜗内细胞以及一些外源性血液和免疫效应细胞中富集。这表明这些细胞类型可能在晚期MD相关的病理过程中起重要作用，为MD病理生理学和治疗的未来研究领域提供了潜在方向。
基于计算机定位，MD中富集的外淋巴蛋白质由特定的耳蜗细胞类型表达，这可能有助于开发疾病特异性诊断标志物和治疗方法。
