Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual Mechanisms of Supporting Cell Regeneration in the Neonatal Mouse Cochlea

ABSTRACT: Cochlear supporting cells are critical for proper hearing function and regeneration of hair cells, which are responsible for perceiving sound in the inner ear. In the neonatal mouse cochlea, when supporting cells are ablated, they can regenerate through progenitor cells in the cochlea. Here, we show through single cell RNA sequencing and in vivo fate mapping, that upon supporting cell ablation in the neonatal cochlea, inner phalangeal cells regenerate through two independent mechanisms; one which requires proliferation and the other by which transdifferentiation (i.e. regeneration without mitotic division) of cochlear progenitor cells occurs. These dual mechanisms are spatially distinct where transdifferentiation occurs in all three turns of the cochlea, while proliferation-induced regeneration occurs exclusively in the apical and middle turns. Inhibiting proliferation using aphidicolin, slightly decreased the number of regenerated IPhCs in the apex middle turns, but not the base, after damage. We also observed a medial to lateral transition in the compartmentalization of the GER after supporting cell damage, suggesting de-differentiation of these domains. Overall, our study reveals GER cells as supporting cell progenitors that undergo dual mechanisms of regeneration (mitotic and non-mitotic). Additionally, we uncover transcriptomic changes after supporting cell damage in the neonatal mouse cochlea that could be used as gene targets in therapies for hearing loss.

ORGANISM(S): Mus musculus

PROVIDER: GSE291228 | GEO | 2026/01/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Characterizing adult cochlear supporting cell transcriptional diversity using single-cell RNA-Seq: Validation in the adult mouse and translational implications for the adult human cochlea

Project description:Characterizing adult cochlear supporting cell transcriptional diversity using scRNA-Seq Hearing loss is a significant disability that impacts 432 million people worldwide. A significant proportion of these individuals are dissatisfied with or do not have access to available treatment options which include hearing aids and cochlear implants. An alternative approach to restore hearing would be to regenerate lost cells, including hair cells in the adult cochlea. Such therapy would require restoration of the organ of Corti’s complex architecture, necessitating regeneration of both mature hair cells and supporting cells. We characterize the first single-cell adult cochlear supporting cell transcriptomes with the goals of: (1) demonstrating their transcriptional distinctiveness from perinatal cochlear supporting cells, (2) providing a metric for future attempts at regenerating mature cochlear supporting cells by identifying both cell type-specific and regional-specific expression, and (3) identify cell cycle gene expression present in adult supporting cells at the single cell level which may establish a basis for targeting cell cycle regulation pathways to force these cells out of quiescence.

2020-02-19 | GSE135703 | 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

Gene expression profiles along the tonotopic axis of the mouse cochlea during neonatal development

Project description:The cochlear duct is tonotopically organized, such that the basal cochlea responds more sensitively to high frequency sounds and the apical cochlea to low frequency sounds. In effort to understand how the tonotopic organization is established in mammals, we searched for genes that are differentially expressed along the tonotopic axis during neonatal development. Eighty temporal bones were dissected from C57BL/6 mice at P0 and P8. The cochlear tissues were divided into three equal pieces representing the basal, middle and apical turns, and pooled separately. Six total RNA from the pooled samples were applied to 6 GeneChips.

2011-12-13 | E-GEOD-34187 | biostudies-arrayexpress

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

scRNA-seq of P2 mouse cochlea

Project description:Purpose and Methods: Cochlear sensory hair cells (HCs) are essential for our sense of hearing. They are embedded in the organ of Corti that lacks regenerative capacity, which is a major cause of hearing loss. However, some neonatal non-sensory cells in the organ of Corti display a limited regenerative ability. We used fluorescence-activated cell sorting (FACS) to isolate different cochlear cell types from postnatal day 2 (P2) mice to assess the individual cell groups’ potential to grow organoids and to generate new HCs. Single-cell RNAseq validated the composition of the cell types in the sorted cell groups. Results and Conclusions: The greater epithelial ridge (GER), a transient tissue that only exists in the neonatal inner ear, harbored the most potent organoid-forming cells. GER-derived organoids expanded into large colonies when cultured adherently and gave rise to new hair cell marker-expressing cells in a sensory epithelia-resembling organization. The organoid forming ability of GER cells was synergistically enhanced when they were cultured at increasing density. The synergistic effect relied on direct cell-to-cell contact rather than released soluble factors.

2020-12-29 | GSE162308 | GEO

Conditional Overexpression of Serpine2 Promotes Hair Cell Regeneration from Lgr5+ Progenitors in the Neonatal Mouse Cochlea

Project description:Neonatal cochlear Lgr5+ progenitors can regenerate hair cells (HCs), and this process is regulated by several genes and signaling pathways. However, this regeneration ability is limited, and whether additional genes are involved in this process remains unknown. Serpine2 was shown to participate in regulating proliferation and differentiation of cochlear Lgr5+ progenitors in our previous in vitro study. Here, we explored the expression pattern and in vivo roles of Serpine2 in HC regeneration by constructing transgenic mice in which Serpine2 is conditionally overexpressed in cochlear Lgr5+ progenitors. We found that Serpine2 is expressed in the mouse cochlea after birth with a downward trend as the mice aged. In addition, Serpine2 conditional overexpression in vivo in Lgr5+ progenitors of neonatal mice cochlea resulted in an increase number of ectopic HCs in a dose-dependent manner. And Serpine2 knockdown ex vivo and in vivo can inhibit HC regeneration. EdU assay and lineage tracing assay demonstrated that these ectopic HCs likely originated from Lgr5+ progenitors through direct trans-differentiation rather than through mitotic regeneration. Moreover, snRNA-seq analysis and RT-qPCR results revealed that Serpine2 cOE likely induces HC regeneration via inhibiting sonic hedgehog (SHH) signal pathway and inducing Atoh1 and Pou4f3 transcription factor. In brief, our data indicate that Serpine2 plays a pivotal role in HC regeneration from Lgr5+ progenitors in the neonatal mouse cochlea, and this suggests a new avenue for future research into HC regeneration.

2025-05-04 | GSE289514 | GEO

Ignition of supporting cell activation for hair cell regeneration in the avian auditory epithelium: an explant culture model

Project description:Sensorineural hearing loss is included in the most common disabilities, and often caused by loss of sensory hair cells in the cochlea. Hair cell regeneration has long been a main target for developing novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration occurs in very limited situations, while auditory epithelia of non-mammalians retain the capacity for hair cell regeneration. In the avian basilar papilla, an auditory sensory epithelium, supporting cells, which are sources for regenerated hair cells, are usually quiescent, while hair cell loss induces both direct transdifferentiation of supporting cells and mitotic division of supporting cells. In the present study, we aimed to establish an explant culture model for hair cell regeneration in chick basilar papillae, and validated usefulness of our model to investigate the initial phase of hair cell regeneration. Histological assessments demonstrated that hair cell regeneration via direct transdifferentiation of supporting cells occurred in our model. Labeling assay using 5-ethynyl-2'-deoxyuridine (EdU) revealed the occurrence of mitotic division of supporting cells in the specific location in basilar papillae, while no EdU labeling was identified in newly generated HCs. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, which is consistent with previous findings. In addition, unbiased analyses of RNA sequencing data indicated novel genes and signaling pathways that could be related to the ignition of supporting cell activation in chick basilar papillae. These results indicate the advantages of our model using explant cultures of chick basilar papillae for exploring molecular mechanisms for hair cell regeneration. Further studies such as single-cell RNA sequencing will allow us to capture the spatiotemporal information by using our explant culture model.

2020-10-23 | GSE154375 | GEO

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

In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated coexpression of Atoh1 and Tbx2

Project description:Cochlear inner hair cells (IHCs) are primary sound receptors, and thus in efforts to develop treatments for hearing impairment. IHC regeneration in vivo has been widely attempted, although not yet in the IHC-damaged cochlea. Moreover, the extent to which new IHCs resemble wild-type IHCs remains unclear, as does whether new IHCs can yield hearing improvement. Here, we developed an in vivo mouse model wherein wild-type IHCs were pre-damaged and nonsensory supporting cells were transformed into IHCs by ectopically expressing Atoh1 transiently and Tbx2 permanently. Notably, the new IHCs expressed the functional marker vGlut3 and presented similar transcriptomic and electrophysiological properties as wild-type IHCs. Furthermore, the formation efficiency and maturity of new IHCs were higher than those previously reported, although marked hearing improvement was not achieved, at least partly due to defective mechanoelectrical transduction (MET) in new IHCs. Thus, we successfully regenerated new IHCs resembling wild-type IHCs in multiple aspects in the damaged cochlea. Our findings suggest that the defective MET is a critical barrier preventing the restoration of hearing capacity and should thus facilitate future IHC regeneration studies.

2023-11-05 | GSE188259 | 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