PDF(Pubmed)
Abstract：
Hair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian cochlear HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). To understand the genetic mechanisms underlying differences among adult zebrafish and mammalian cochlear HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. For example, both zebrafish and mouse HCs express Tmc1, Lhfpl5, Tmie, Cib2, Cacna1d, Cacnb2, Otof, Pclo and Slc17a8. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type. Tmc2 and Cib3 were not detected in adult mouse HCs but tmc2a and b and cib3 were highly expressed in zHCs. Mouse HCs express Kcna10, Kcnj13, Kcnj16, and Kcnq4, which were not detected in zHCs. Chrna9 and Chrna10 were expressed in mouse HCs. In contrast, chrna10 was not detected in zHCs. OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of slc26a5, and subsequently showed no voltage dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.
摘要：
毛细胞（HC）是脊椎动物内耳中听觉和前庭系统的感觉受体，可将机械刺激选择性地转化为电活动。尽管所有HC都具有机械转导的标志性立体纤毛束，非哺乳动物和哺乳动物中的HCs在顶端的分子专业化方面有所不同，基底外侧和突触膜。非哺乳动物的HCs，如斑马鱼（zHCs），被电调谐到特定频率，并在立体纤毛束中具有主动过程以放大声音信号。哺乳动物耳蜗HC，相比之下,不进行电调谐，并通过外部HC（OHC）的体细胞运动性实现扩增。为了了解成年斑马鱼和哺乳动物耳蜗HCs之间差异的遗传机制，我们比较了他们的RNA-seq特征转录组，专注于与HC特化相关的蛋白质编码直系同源基因。在HC之间有相当多的基因直向同源物的共享表达，包括那些与机械转导相关的基因，离子传输/通道，和突触信号。例如,斑马鱼和小鼠HCs都表达Tmc1，Lhfpl5，Tmie，Cib2,Cacna1d,Cacnb2,Otof,Pclo和Slc17a8。然而,zHCs之间的表达有一些显着差异，OHCs,和内部HC(IHC)，这可能是每种细胞类型独特的生理特性的基础。在成年小鼠HCs中未检测到Tmc2和Cib3，但tmc2a和b和Cib3在zHCs中高度表达。小鼠HCs表达Kcna10,Kcnj13,Kcnj16,和Kcnq4，在zHCs中未检测到。Chrna9和Chrna10在小鼠HC中表达。相比之下,在zHCs中未检测到chrna10。OHC高度表达Slc26a5，其编码有助于OHC电动性的运动蛋白prestin。然而,zHCs仅弱表达slc26a5，并随后在测量时显示没有电压依赖性的电运动性。值得注意的是,zHC表达更多的旁系同源基因，包括与HC特异性功能和转录活性相关的基因，尽管尚不清楚它们是否具有与哺乳动物对应物相似的功能。与已知听力表型相关的表达基因存在重叠。我们的分析揭示了基因表达模式的实质性差异，这可能解释了斑马鱼和小鼠HCs的表型特化。该数据集还包括几个蛋白质编码基因，以进一步表征HC的功能并研究HC从非哺乳动物到哺乳动物的进化。
