Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ScRNA-seq of P2 mouse cochlea

ABSTRACT: Age-related hearing impairment (ARHI), one of the most common medical conditions, is strongly heritable, yet its genetic causes remain largely unknown. We conducted a meta-analysis of GWAS summary statistics from multiple hearing-related traits in the UK Biobank (n = up to 323,978) and identified 31 genome-wide significant risk loci for self-reported hearing difficulty (p < 5e-8), of which 30 have not been reported previously at genome-wide significance. We interpreted these loci in the context of newly generated ATAC-seq and single-cell RNA-seq from cells in the mouse cochlea. Risk-associated genes were enriched for expression in cochlear epithelial and non-epithelial cells, as well as for genes related to sensory perception and known Mendelian deafness genes, supporting their relevance to auditory function. Regions of the human genome homologous to open chromatin in sensory epithelial cells from the mouse were strongly enriched for heritable risk for hearing difficulty, even after adjusting for baseline effects of evolutionary conservation and cell-type non-specific regulatory regions. Epigenomic and statistical fine-mapping most strongly supported 50 putative risk genes. Of these, at least 45 were expressed in mouse cochlea and 15 were enriched specifically in sensory hair cells. These results reveal new risk loci and risk genes for hearing difficulty and suggest an important role for altered gene regulation in the cochlear sensory epithelium.

ORGANISM(S): Mus musculus

PROVIDER: GSE135737 | GEO | 2020/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteome Comparison of Different-Aged Cochlea

Project description:Our work describes the application of mass spectrometry-based label-free quantitative proteomics for the identification of differentially expressed proteins between different-aged cochlea. We report proteins exclusively present as well as up- and downregulated in the cochlear sensory epithelium at significant developmental stages. Additionally, we report proteins exclusively present on P3 that were recently identified in the cochlea for the first time. We use bioinformatics to provide insight on biological functions and potential primary and secondary partners of the differentially expressed proteins. This study provides the first differentially expressed proteome in the mammalian cochlea at significant developmental stages; before hearing, during the onset of hearing, and when hearing is fully developed. We believe that these results will provide insights into the function of proteins that change during development and identify potential protein biomarkers related to hearing impairments.

2018-08-29 | PXD001973 | Pride

Unraveling the Molecular Landscape of Lead-Induced Cochlear Synaptopathy: A Quantitative Proteomic Analysis

Project description:This study investigates how lead exposure triggers cochlear synaptopathy and hearing loss in mice. Young-adult CBA/J mice were given lead acetate in drinking water for 28 days. We assessed hearing thresholds, outer hair cell activity, and synaptic changes in the cochlea. Lead exposure raises hearing thresholds, indicating cochlear synaptopathy. Notably affects synapses in the basal turn without impacting outer hair cells. In addition to this, lead altered the abundance of 352 synaptic proteins, with the synaptic vesicle cycle pathway prominently affected. Lead-induced cochlear synaptopathy targets basal cochlear regions, implicating synaptic vesicle cycle signaling in hearing loss. Revealing specific mechanisms behind lead-induced hearing deficits enhances targeted interventions and preventive strategies, advancing our understanding of lead induced hearing loss.

2024-10-17 | PXD050415 | Pride

Cochlear transcriptome at 3 hours post-noise trauma in mice

Project description:In order to elucidate molecular mechanisms of noise-induced hearing loss in the cochlea (inner ear), transcriptome of the cochlear sample was analyzed after induction of hearing loss by exposure to intense noise in mice. Cochlear transcriptome was analyzed at 3 hours following the noise exposure.

2020-01-14 | GSE137817 | GEO

Ptch1/Shh signaling control cochlear marginal cell differentiation and stria vascularis formation

Project description:The stria vascularis (SV) is an intricate non-sensory structure composed of multiple cell layers of different origins in the mammalian cochlea. It generates and maintains the endolymph, and therefore is essential for hearing functions. Here, using single cell transcriptomics and transgenic mouse models, we discover that the Shh receptor Ptch1 is required for marginal cell (MC, the epithelial cell layer of SV) differentiation and SV development. During cochlear development, MC differentiation gradually proceeds from cochlear base to apex, resembling the spatiotemporal differentiation pattern of sensory hair cells. Inactivation of Ptch1 leads to an impaired MC differentiation through elevated Gli2 levels, and inhibition of Gli2/Shh signaling activity is a prerequisite for MC differentiation. Single cell transcriptome analyses reveal that MCs are specified as early as E14. Moreover, in the absence of Ptch1, MC precursors are maintained in the progenitor state and differentiation is blocked consequently.

2024-04-03 | GSE217373 | GEO

Cochlear transcriptome after noise trauma and dexamethasone therapy in mice

Project description:In order to elucidate molecular mechanisms of noise-induced hearing loss and dexamethasone therapy in the cochlea (inner ear), transcriptome of cochlear samples was analyzed after induction of hearing loss by exposure to intense noise in mice. Dexamethasone was intraperitoneally injected immediately following the noise trauma. Cochlear transcriptome was analyzed at 12h and 24h following the noise trauma and dexamethasone administration.

2016-12-03 | GSE85290 | GEO

Redox activation of excitatory pathways in auditory neurons as mechanism of age-related hearing loss

Project description:Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL.

2020-12-18 | E-MTAB-8668 | biostudies-arrayexpress

Ebf1 is a mouse deafness gene and deletion causes a dramatic increase in hair cells and support cells of the organ of Corti

Project description:Following up on our previous observation that early B cell factor (EBF) sites are enriched in open chromatin of the developing sensory epithelium of the mouse cochlea, we investigated the effect of deletion of Ebf1 on inner ear development. We used a Cre driver to delete Ebf1 at the otocyst stage prior to development of the cochlea. These animals survived and were fertile. We examined the cochlea at postnatal day (P) 1 and found that the sensory epithelium had doubled in size but the length of the cochlear duct was unaffected. We also found that deletion of Ebf1 led to ectopic sensory patches in the Kölliker’s organ. Innervation of the developing organ of Corti was disrupted with no obvious spiral bundles. The ectopic patches were also innervated. All the extra hair cells (HCs) within the sensory epithelium and Kölliker’s organ contained mechanoelectrical transduction channels as indicated by rapid uptake of FM1-43. The excessive numbers of HCs were still present in the adult Ebf1 conditional knockout (cKO) animal. The animals had no detectable auditory brainstem response (ABR) suggesting that this gene is essential for hearing development.

2024-02-26 | GSE256327 | GEO

Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

Project description:This study demonstrates the baseline data of gradient gene expression in the cochlea. Especially for genes whose mutations cause autosomal dominant non syndromic hearing loss (Pou4f3, Slc17a8, Tmc1, and Crym) as well as genes important for cochlear function (Emilin-2 and Tectb), gradual expression changes help to explain the various pathological conditions. Four C57BL/6 mice aged 6 weeks cochlea samples including the lateral wall, stria vascularis, spiral ligament, spiral prominence, and the organ of corti were dissected and separated into the apical, middle and basal turns to compare gene expression profiles of each cochlea turn.

2014-01-08 | E-GEOD-53863 | biostudies-arrayexpress

Molecular changes associated with biological aging of cochlear hair cells

Project description:Age-related hearing loss (ARHL) is a progressive sensorineural hearing loss that occurs as people get older. As many as 35% to 50% of the population aged between 65 and 75 have ARHL. Although age-related changes in the central auditory system can contribute to hearing impairment, degeneration of the mechanosensitive hair cells in the cochlea is the prevalent cause of ARHL. The molecular mechanisms of hair cell aging are largely unknown. To provide a comprehensive dataset of age-related genes and pathways in hair cells, we individually collected inner and outer hair cells, the two types of sensory receptor cells in the cochlea, from 9- and 26-month-old CBA/J mice and performed cell type-specific transcriptomic analysis. Our analysis showed a significant reduction of the expression of genes related to hair cell structure and function such as Tmc1, Kcnq4, Kcnj13, Slc7a14, Slc17a8, Chrna9/Chrna10, and Slc26a5. Our hair cell-specific transcriptome analysis provides a rich resource for mechanistic studies of biological aging of cochlear hair cells.

2022-03-01 | GSE153882 | GEO

Pseudo-temporal analysis of Single-cell RNA sequencing reveals trans-differentiation potential of Greater Epithelial Ridge cells into hair cells during postnatal development of cochlea in Rats

Project description:The hair cells of the cochlea play a decisive role in the process of hearing damage and recovery, yet knowledge of their regeneration process is still limited. Greater epithelial ridge (GER) cells, a type of cell present during cochlear development that has the characteristics of a precursor sensory cell, disappear at the time of maturation of hearing development. Its development and evolution remain mysterious for many years. Here, we performed single-cell RNA sequencing to profile the gene expression landscapes of rats' cochlear duct from P1, P7, and P14 and identified eight major subtypes of GER cells. Furthermore, single-cell trajectory analysis for GER cells and hair cells indicated that among the different subtypes of GER, four subtypes had transient cell proliferation after birth and could transdifferentiate into inner and outer hair cells, and two of them mainly transdifferentiated into inner hair cells. The other two subtypes eventually transdifferentiate into outer hair cells. Our study lays the groundwork for elucidating the mechanisms of the key regulatory genes and signaling pathways in the trans-differentiation of GER cell subtypes into hair cells and provides potential clues to understand hair cell regeneration.

2022-01-29 | GSE195702 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data