Giffen Kimberlee P, Liu Huizhan, Yamane Kacey L, Li Yi, Chen Lei, Kramer Ken L, Zallocchi Marisa, He David Z Z
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Augusta University/University of Georgia Medical Partnership, Athens, GA, USA.
bioRxiv. 2024 May 26:2024.05.24.595729. doi: 10.1101/2024.05.24.595729.
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 and . 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. were not detected in adult mouse HCs but and and were highly expressed in zHCs. Mouse HCs express , , , and , which were not detected in zHCs. and were expressed in mouse HCs. In contrast, was not detected in zHCs. OHCs highly express which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of , 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.
毛细胞（HCs）是脊椎动物内耳听觉和前庭系统的感觉感受器，可将机械刺激选择性地转换为电活动。尽管所有毛细胞都具有用于机械转导的标志性静纤毛束，但非哺乳动物和哺乳动物的毛细胞在其顶端、基底外侧和突触膜的分子特化方面存在差异。非哺乳动物的毛细胞，如斑马鱼的毛细胞（zHCs），会被电调谐到特定频率，并在静纤毛束中具有一个主动过程来放大声音信号。相比之下，哺乳动物耳蜗毛细胞不会被电调谐，而是通过外毛细胞（OHCs）的体细胞运动来实现放大。为了了解成年斑马鱼和哺乳动物耳蜗毛细胞之间差异的遗传机制，我们比较了它们通过RNA测序表征的转录组，重点关注与毛细胞特化相关的蛋白质编码直系同源基因。毛细胞之间存在相当多的基因直系同源物共享表达，包括那些与机械转导、离子运输/通道和突触信号相关的基因。例如，斑马鱼和小鼠的毛细胞都表达 和 。然而，zHCs、OHCs和内毛细胞（IHCs）之间在表达上存在一些显著差异，这可能是每种细胞类型独特生理特性的基础。在成年小鼠毛细胞中未检测到 ，但 在zHCs中高度表达。小鼠毛细胞表达 、 、 和 ，而在zHCs中未检测到这些基因。 和 在小鼠毛细胞中表达。相比之下，在zHCs中未检测到 。OHCs高度表达 ，该基因编码有助于OHC电运动的运动蛋白prestin。然而，zHCs中 的表达较弱，随后在测量时未表现出电压依赖性电运动。值得注意的是，zHCs表达了更多的旁系同源基因，包括那些与毛细胞特异性功能和转录活性相关的基因，尽管它们是否具有与其哺乳动物对应物相似的功能尚不清楚。在与已知听力表型相关的表达基因中存在重叠。我们的分析揭示了基因表达模式的显著差异，这可能解释了斑马鱼和小鼠毛细胞的表型特化。该数据集还包括几个蛋白质编码基因，以进一步了解毛细胞的功能特征以及研究从非哺乳动物到哺乳动物的毛细胞进化。
