The Genomics of Auditory Function and Disease

Taiber, Shahar; Gwilliam, Kathleen; Hertzano, Ronna; Avraham, Karen B.

doi:10.1146/annurev-genom-121321-094136

Cited by 13 publications

(8 citation statements)

References 195 publications

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“…Epigenetic modifications have recently been found to contribute to inner ear development and HC regeneration (Taiber et al, 2022 ). Histone methylation and demethylation are implicated in transcriptional regulation, genome integrity, and epigenetics (Klose and Zhang, 2007 ).…”

Section: Resultsmentioning

confidence: 99%

Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage

Zou

et al. 2023

Front. Mol. Neurosci.

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Cisplatin is widely used in clinical tumor chemotherapy but has severe ototoxic side effects, including tinnitus and hearing damage. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. In this study, we used CBA/CaJ mice to establish an ototoxicity model of cisplatin-induced hair cell loss, and our results showed that cisplatin treatment could reduce FOXG1 expression and autophagy levels. Additionally, H3K9me2 levels increased in cochlear hair cells after cisplatin administration. Reduced FOXG1 expression caused decreased microRNA (miRNA) expression and autophagy levels, leading to reactive oxygen species (ROS) accumulation and cochlear hair cell death. Inhibiting miRNA expression decreased the autophagy levels of OC-1 cells and significantly increased cellular ROS levels and the apoptosis ratio in vitro. In vitro, overexpression of FOXG1 and its target miRNAs could rescue the cisplatin-induced decrease in autophagy, thereby reducing apoptosis. BIX01294 is an inhibitor of G9a, the enzyme in charge of H3K9me2, and can reduce hair cell damage and rescue the hearing loss caused by cisplatin in vivo. This study demonstrates that FOXG1-related epigenetics plays a role in cisplatin-induced ototoxicity through the autophagy pathway, providing new ideas and intervention targets for treating ototoxicity.

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Section: Resultsmentioning

confidence: 99%

Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage

Zou

et al. 2023

Front. Mol. Neurosci.

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“…For example, evidence suggests that a number of transcription factors such as DLX5 , SIX1 , and GATA2 are associated with hearing loss and/or vestibular dysfunction and many Online Mendelian Inheritance in Man ® genes have been linked to deafness and vestibular disorders (Merlo et al, 2002; Zheng et al, 2003; Haugas et al, 2010; Ramirez-Gordillo et al. 2015; Taiber et al, 2022). However, in comparison with other organ systems such as the eye, heart, and kidney, far less is known about the inner ear’s developmental transcriptome, and the control of genetic networks that typify inner ear development (Giraldez and Fritzsch, 2007; Broto et al, 2021; Mackowetzky et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis Identifies Candidate Genes for Differential Expression duringXenopus laevisInner Ear Development

Virk,

Trujillo-Provencio,

Serrano

2024

Preprint

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Background.The genes involved in inner ear development and maintenance of the adult organ have yet to be fully characterized. Previous genetic analysis has emphasized the early development that gives rise to the otic vesicle. This study aimed to bridge the knowledge gap and identify candidate genes that are expressed as the auditory and vestibular sensory organs continue to grow and develop until the systems reach postmetamorphic maturity.Methods.Affymetrix microarrays were used to assess inner ear transcriptome profiles from threeXenopus laevisdevelopmental ages where all eight endorgans comprise mechanosensory hair cells: larval stages 50 and 56, and the post-metamorphic juvenile. Pairwise comparisons were made between the three developmental stages and the resulting differentially expressedX. laevisProbe Set IDs (Xl-PSIDs) were assigned to four groups based on differential expression patterns. DAVID analysis was undertaken to impart functional annotation to the differentially regulated Xl-PSIDs.Results.Analysis identified 1510 candidate genes for differential gene expression in one or more pairwise comparison. Annotated genes not previously associated with inner ear development emerged from this analysis, as well as annotated genes with established inner ear function, such as oncomodulin, neurod1, and sp7. Notably, 36% of differentially expressed Xl-PSIDs were unannotated.Conclusions.Results draw attention to the complex gene regulatory patterns that characterizeXenopusinner ear development, and underscore the need for improved annotation of theX. laevisgenome. Outcomes can be utilized to select candidate inner ear genes for functional analysis, and to promoteXenopusas a model organism for biomedical studies of hearing and balance.

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“…Although hearing loss can target different cell types within the auditory pathway (e.g. [17][18][19]), one of the most common forms of hearing loss is caused by the damage and/or loss of the sensory hair cells and the associated auditory neurons that make synaptic connections within the cochlea, which is collectively called sensorineural hearing loss (SNHL: [8,[20][21][22]). Currently, the only available options for ameliorating SNHL are hearing aids or cochlear implants.…”

Section: Introductionmentioning

confidence: 99%

Recent advances and future challenges in gene therapy for hearing loss

et al. 2023

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Hearing loss is the most common sensory deficit experienced by humans and represents one of the largest chronic health conditions worldwide. It is expected that around 10% of the world's population will be affected by disabling hearing impairment by 2050. Hereditary hearing loss accounts for most of the known forms of congenital deafness, and over 25% of adult-onset or progressive hearing loss. Despite the identification of well over 130 genes associated with deafness, there is currently no curative treatment for inherited deafness. Recently, several pre-clinical studies in mice that exhibit key features of human deafness have shown promising hearing recovery through gene therapy involving the replacement of the defective gene with a functional one. Although the potential application of this therapeutic approach to humans is closer than ever, substantial further challenges need to be overcome, including testing the safety and longevity of the treatment, identifying critical therapeutic time windows and improving the efficiency of the treatment. Herein, we provide an overview of the recent advances in gene therapy and highlight the current hurdles that the scientific community need to overcome to ensure a safe and secure implementation of this therapeutic approach in clinical trials.

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The Genomics of Auditory Function and Disease

Cited by 13 publications

References 195 publications

Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage

Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage

Transcriptomic Analysis Identifies Candidate Genes for Differential Expression duringXenopus laevisInner Ear Development

Recent advances and future challenges in gene therapy for hearing loss

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