Integrative Functional Transcriptomic Analyses Implicate Shared Molecular Circuits in Sensorineural Hearing Loss

Chen, Peng; Hao, Jiejie; Li, Mengwen; Bai, Jing; Guo, Yuan-Ting; Liu, Zhen; Shi, Peng

doi:10.3389/fncel.2022.857344

Cited by 3 publications

(4 citation statements)

References 55 publications

(64 reference statements)

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“…1C ). These results closely align with those reported by Chen et al [ 22 ], who revealed that a mouse model based on aging, noise exposure, and cisplatin ototoxicity shared hub genes involved in immune system processes, the inflammatory response, and apoptotic processes. Similarly, the 79 upregulated mRNAs identified in this study were involved in defense and immune responses.…”

Section: Discussionsupporting

confidence: 92%

Identification and Characterization of mRNA and lncRNA Expression Profiles in Age-Related Hearing Loss

Kim¹,

Lee²,

Lee³

et al. 2023

Clin Exp Otorhinolaryngol

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Objectives. Age-related hearing loss (ARHL), or presbycusis, is caused by disorders of sensory hair cells and auditory neurons. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, noise, inflammation, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Long non-coding RNA (lncRNA) has been reported to play important roles in various diseases. However, the function of lncRNA in ARHL remains unclear. In this study, we analyzed the common expression profiles of messenger RNA (mRNA) and lncRNA through ARHL-related RNA-sequencing datasets.Methods. We selected and downloaded three different sets of RNA-sequencing data for ARHL. We performed differential expression analysis to find common mRNA and lncRNA profiles in the cochleae of aged mice compared to young mice. Gene Ontology (GO) analysis was used for functional exploration. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to validate mRNAs and lncRNAs. In addition, we performed trans target prediction analysis with differentially expressed mRNAs and lncRNAs to understand the function of these mRNAs and lncRNAs in ARHL.Results. We identified 112 common mRNAs and 10 common lncRNAs in the cochleae of aged mice compared to young mice. GO analysis showed that the 112 upregulated mRNAs were enriched in the defense response pathway. When we performed qRT-PCR with 1 mM H2O2-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, the qRT-PCR results were consistent with the RNA-sequencing analysis data. lncRNA-mRNA networks were constructed using the 10 common lncRNAs and 112 common mRNAs in ARHL.Conclusion. Our study provides a comprehensive understanding of the common mRNA and lncRNA expression profiles in ARHL. Knowledge of ARHL-associated mRNAs and lncRNAs could be useful for better understanding ARHL and these mRNAs and lncRNAs might be a potential therapeutic target for preventing ARHL.

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Section: Discussionsupporting

confidence: 92%

Identification and Characterization of mRNA and lncRNA Expression Profiles in Age-Related Hearing Loss

Kim¹,

Lee²,

Lee³

et al. 2023

Clin Exp Otorhinolaryngol

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“…Research on bulk data and single-cell transcriptomics related to sensory neural hearing loss currently mainly focuses on inner ear hair cells. Studies have found that major causal factors inducing sensory neural hearing loss, such as aging, noise, and drug-related factors, share common pathways for damage to inner ear hair cells: apoptosis, the immune response, and inflammation [ 19 ]. The changes observed in OHCs during aging and in response to noise exposure involve common processes, including the immune response, cellular response to stress, regulation of transmembrane transport, and ion channel regulation.…”

Section: Discussionmentioning

confidence: 99%

“…Bulk data from three models showed that gene coexpression in inflammation, immunity, apoptosis and ion transport significantly correlated with each other in the hair cells of the cochlea [ 17 , 18 ]. Increasing inflammatory factors IL1B and CCL2 inducing ROS-related apoptosis in the whole cochleae of SNHL were identified by previous studies in vitro and vivo [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Gu,

Jiang,

Chen

et al. 2024

BMC Genomics

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Background The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. Methods We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. Results Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. Conclusion Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL.

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“…Substantial evidence suggested that the metabolism of the fatty acids played a crucial role in maintaining the inner ear and vestibule cellular mechanisms and were involved in hearing and balance system development ( Fujita et al, 2015 ; Pirttilä et al, 2019 ). Moreover, the inner ear was a high energy consumption organ whose demands on energy supply were enormous ( Chen et al, 2022c ). When glucose metabolism cannot meet the energy supply in the inner ear under physiological or pathological conditions, fatty acid oxidation will be enhanced ( Chen et al, 2022d ; Wang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients

Wang

Gao

Jiang

2022

Front. Mol. Biosci.

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Sudden sensorineural hearing loss (SSNHL) is an otologic emergency, and metabolic disturbance is involved in its pathogenesis. This study recruited 20 SSNHL patients and 20 healthy controls (HCs) and collected their serum samples. Serum metabolites were detected by liquid chromatography-mass spectrometry, and metabolic profiles were analyzed. All patients were followed up for 3 months and categorized into recovery and non-recovery groups. The distinctive metabolites were assessed between two groups, and their predictive values for hearing recovery were evaluated. Analysis results revealed that SSNHL patients exhibited significantly characteristic metabolite signatures compared to HCs. The top 10 differential metabolites were further analyzed, and most of them showed potential diagnostic values based on receiver operator characteristic (ROC) curves. Finally, 14 SSNHL patients were divided into the recovery group, and six patients were included in the non-recovery group. Twelve distinctive metabolites were observed between the two groups, and ROC curves demonstrated that N4-acetylcytidine, p-phenylenediamine, sphingosine, glycero-3-phosphocholine, and nonadecanoic acid presented good predictabilities in the hearing recovery. Multivariate analysis results demonstrated that serum N4-Acetylcytidine, sphingosine and nonadecanoic acid levels were associated with hearing recovery in SSNHL patients. Our results identified that SSNHL patients exhibited distinctive serum metabolomics signatures, and several serum biomarkers were proved to be potential in predicting hearing recovery. The discriminative metabolites might contribute to illustrating the mechanisms of SSNHL and provide possible clues for its treatments.

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Integrative Functional Transcriptomic Analyses Implicate Shared Molecular Circuits in Sensorineural Hearing Loss

Cited by 3 publications

References 55 publications

Identification and Characterization of mRNA and lncRNA Expression Profiles in Age-Related Hearing Loss

Identification and Characterization of mRNA and lncRNA Expression Profiles in Age-Related Hearing Loss

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients

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