一种用于阐明miR-96在内耳毛细胞中作用的细胞类型特异性方法。

A cell type-specific approach to elucidate the role of miR-96 in inner ear hair cells.

作者信息

Gwilliam Kathleen, Sperber Michal, Perry Katherine, Rose Kevin P, Ginsberg Laura, Paladugu Nikhil, Song Yang, Milon Beatrice, Elkon Ran, Hertzano Ronna

机构信息

Section on Omics and Translational Science of Hearing, Neurotology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States.

Department of Human Molecular Genetics and Biochemistry, Tel Aviv University School of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Front Audiol Otol. 2024;2. doi: 10.3389/fauot.2024.1400576. Epub 2024 May 9.

Abstract

INTRODUCTION

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 heterozygous, homozygous mutant, and wildtype mice.

METHODS

Bulk RNA-seq was performed on HCs of newborn heterozygous, homozygous mutant, and wildtype mice. Differentially expressed gene analysis was conducted on homozygous mutant HCs compared to wildtype littermate controls, followed by GO term and protein-protein interaction analysis on these differentially expressed genes.

RESULTS

We identify 215 upregulated and 428 downregulated genes in the HCs of the homozygous mutant mice compared to their wildtype littermate controls. Many of the significantly downregulated genes in homozygous mutant HCs have established roles in HC development and/or known roles in deafness including , and and have enrichment in gene ontology (GO) terms with biological functions such as sensory perception of sound. Interestingly, upregulated genes in homozygous mutants, including possible miR-96 direct targets, show higher wildtype expression in supporting cells compared to HCs.

CONCLUSION

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 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).

摘要

引言

微小RNA-96(miR-96)在小鼠内耳毛细胞(HCs)中表达,其突变会导致小鼠模型和人类出现进行性听力损失。在本研究中,我们展示了来自新生杂合子、纯合突变体和野生型小鼠的首个毛细胞特异性RNA测序(RNA-seq)数据集。

方法

对新生杂合子、纯合突变体和野生型小鼠的毛细胞进行大量RNA测序。对纯合突变体毛细胞与野生型同窝对照进行差异表达基因分析,随后对这些差异表达基因进行基因本体(GO)术语和蛋白质-蛋白质相互作用分析。

结果

与野生型同窝对照相比,我们在纯合突变体小鼠的毛细胞中鉴定出215个上调基因和428个下调基因。纯合突变体毛细胞中许多显著下调的基因在毛细胞发育中具有既定作用和/或在耳聋中具有已知作用,包括……并且在具有诸如声音感觉感知等生物学功能的基因本体(GO)术语中富集。有趣的是,纯合突变体中的上调基因,包括可能的miR-96直接靶点,与毛细胞相比,在支持细胞中显示出更高的野生型表达。

结论

我们的数据进一步支持miR-96在毛细胞发育中的作用,可能作为毛细胞中支持细胞转录程序的抑制因子。本论文生成的毛细胞特异性RNA-seq数据集现已在基因表达分析资源(gEAR-https://umgear.org/p?l=miR96)的专用档案中公开提供。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff2d/11141775/dc23daff0807/nihms-1993125-f0001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索