用细胞特异性方法阐明 miR-96 在内耳毛细胞中的作用

Kathleen Gwilliam, M. Sperber, Katherine Perry, Kevin P. Rose, Laura Ginsberg, Nikhil Paladugu, Yang Song, B. Milon, Ran Elkon, R. Hertzano
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引用次数: 0

摘要

microRNA-96(miR-96)是一种在内耳毛细胞(HC)中表达的微RNA,它的突变会导致小鼠模型和人类的渐进性听力损失。在这项研究中,我们首次展示了来自新生 Mir96Dmdo 杂合子、同源突变体和野生型小鼠的 HC 特异性 RNA 序列(RNA-seq)数据集。与野生型同窝对照组相比,我们对Mir96Dmdo同源突变小鼠的HC进行了差异表达基因分析,然后对这些差异表达基因进行了GO项和蛋白质-蛋白质相互作用分析。在Mir96Dmdo同源突变体HC中,许多明显下调的基因在HC发育中发挥着既定的作用和/或在耳聋中发挥着已知的作用,这些基因包括Myo15a、Myo7a、Ush1c、Gfi1和Ptprq,并且在基因本体(GO)术语中富集了声音感知等生物功能。有趣的是,在 Mir96Dmdo 基因同源突变体中,包括可能的 miR-96 直接靶标在内的上调基因在支持细胞中的野生型表达高于 HCs。本稿件中生成的HC特异性Mir96Dmdo RNA-seq数据集现已在基因表达分析资源(gEAR-https://umgear.org/p?l=miR96)中的一个专用档案中公开。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A cell type–specific approach to elucidate the role of miR-96 in inner ear hair cells
Mutations in microRNA-96 (miR-96), a microRNA expressed within the hair cells (HCs) of the inner ear, result in progressive hearing loss in both mouse models and humans. In this study, we present the first HC-specific RNA-sequencing (RNA-seq) dataset from newborn Mir96Dmdo heterozygous, homozygous mutant, and wildtype mice.Bulk RNA-seq was performed on HCs of newborn Mir96Dmdo heterozygous, homozygous mutant, and wildtype mice. Differentially expressed gene analysis was conducted on Mir96Dmdo homozygous mutant HCs compared to wildtype littermate controls, followed by GO term and protein-protein interaction analysis on these differentially expressed genes.We identify 215 upregulated and 428 downregulated genes in the HCs of the Mir96Dmdo homozygous mutant mice compared to their wildtype littermate controls. Many of the significantly downregulated genes in Mir96Dmdo homozygous mutant HCs have established roles in HC development and/or known roles in deafness including Myo15a, Myo7a, Ush1c, Gfi1, and Ptprq and have enrichment in gene ontology (GO) terms with biological functions such as sensory perception of sound. Interestingly, upregulated genes in Mir96Dmdo homozygous mutants, including possible miR-96 direct targets, show higher wildtype expression in supporting cells compared to HCs.Our data further support a role for miR-96 in HC development, possibly as a repressor of supporting cell transcriptional programs in HCs. The HC-specific Mir96Dmdo RNA-seq data set generated from this manuscript are now publicly available in a dedicated profile in the gene expression analysis resource (gEAR-https://umgear.org/p?l=miR96).
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