Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor, a candidate mediator of hearing restoration mechanisms
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA837539 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19177600.fastq.gz | Fastqsanger.gz | |||
| SRR19177700.fastq.gz | Fastqsanger.gz | |||
| SRR19177800.fastq.gz | Fastqsanger.gz | |||
| SRR19177601.fastq.gz | Fastqsanger.gz | |||
| SRR19177701.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 354 |
Similar Datasets
Project description:One potential approach to restore hearing is to enforce regeneration of hair cells (HCs) through induction of cellular signaling pathways in supporting cells (SCs) that promote dedifferentiation and proliferation. We previously showed that the constitutive activation of ERBB2 signaling in cochlear SCs indirectly promoted SC differentiation to HCs, both in vivo and in vitro. In the current study, we aimed at identifying mechanisms and molecular pathways activated in SCs with constitutive ERBB2 signaling. To this end, we used single cell RNA sequencing (scRNA-seq) to characterize the transcriptomes of individual neonatal mouse cochlear SCs that were induced to express ERBB2. We found that induction of ERBB2 in vivo resulted in generation of a new distinct cluster of cells with unique transcriptome. This population has de novo expression of two members of the small integrin-binding ligand n-linked glycoproteins (SIBLING) family and their regulators. We confirm expression of the SIBLING Secreted phosphoprotein 1 (SPP1) as one of the most up-regulated genes in response to ERBB2 activation. SPP1 mediates signaling through the CD44 receptor, promoting survival, proliferation, and differentiation of osteoblast lineage cells. Histological analyses of cochlear samples collected from young adult mice confirmed that induction of ERBB2 after noise exposure resulted in up-regulation of both SPP1 and its receptor CD44, and the formation of mitotic sensory stem-like cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2-signaling in young adult mice secondarily promotes SPP1/CD44 signaling, possibly altering the microenvironment of the organ of Corti.
2022-12-13 | GSE202850 | GEO
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
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 1 and postnatal day 6. mRNA profiles of supporting cells (GFP+) and all other cochlear cell types (GFP-), two replicates each, at P1 and P6 mice were generated by deep sequencing using Illumna TruSeq.
2016-07-01 | E-GEOD-83356 | biostudies-arrayexpress
Project description:Mammalian cochlear outer hair cells (OHCs) are essential for hearing. Severe hearing impairment follows OHC degeneration. Previous attempts at regenerating new OHCs from cochlear supporting cells (SCs) have been unsuccessful, notably lacking expression of the key OHC motor protein, Prestin. Thus, regeneration of Prestin+ OHCs represented a barrier to restoring auditory function in vivo. Here, we reported the successful in vivo conversion of adult mouse cochlear SCs into Prestin+ OHC-like cells through the concurrent induction of two key transcriptional factors known to be necessary for OHC development: Atoh1 and Ikzf2. Single cell RNA sequencing reveals the upregulation of 729 OHC genes and downregulation of 331 SC genes in OHC-like cells. The resulting differentiation status of these OHC-like cells was much more advanced than previously achieved. This study thus established an efficient approach to induce the regeneration of Prestin+ OHCs, paving the way for in vivo cochlear repair via SC transdifferentiation.
2021-09-03 | GSE161156 | GEO
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
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6 after inhibition of the Notch signaling pathway. Cochleas from postnatal day 0 and postnatal day 5 were cultured for 24 hours in the gamma secretase inhibitor DAPT or DMSO as a vehicle control. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 0+24 hours culture and postnatal day 5 + 24 hours culture. (corresponding to P1 and P6). mRNA profiles of P0 and P5 supporting cells (GFP+) and all other cochlear cell types (GFP-) treated with DAPT or DMSO, two replicates each, were generated by deep sequencing using Illumna TruSeq.
2016-07-01 | E-GEOD-83340 | biostudies-arrayexpress
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 1 and postnatal day 6.
2016-07-01 | GSE83356 | GEO
Project description:The cochlea, a sensitive biosensor, detects sound waves and converts them into electrical signals the brain recognizes as sound. Damage to cochlear hair cells can release proteins, triggering biological responses that may impair hearing. Mass spectrometry-based proteomics offers insights into protein expression changes in cochlear tissues, improving our understanding of inner ear diseases. In this study, we performed a comprehensive proteomics analysis of whole cochlear tissue extracted from healthy guinea pigs and rats. The study optimized protein extraction protocols and analyzed cochlear protein expression using three biological replicates for each animal model. This work optimized protein extraction protocols and analyzed cochlear protein expression using three biological replicates for each animal model. The results identified 1801 proteins in guinea pigs and 3867 proteins in rats, with a high overlap in cochlear protein expression between the left and right ears—93% in guinea pigs and 89% in rats. The findings validate the assumption that the cochlear tissues from both sides of the ears can be considered biologically equivalent. This experiment provides a comprehensive cochlear proteome for guinea pigs and rats, supporting future studies on inner ear disorders.
2025-07-21 | PXD059025 | Pride
Project description:Regeneration enables organisms to repair damaged tissues, yet this capacity is strikingly limited in the cochlear sensory epithelium, essential for sound detection. A major cause of hearing loss arises from the irreversible loss of sensory hair cells (HCs) in the cochlea. While supporting cells (SCs) have a latent ability to trans-differentiate into HCs, this regenerative potential is rapidly lost after development. Using live imaging and single-cell multiomics of cochlear explants, we uncovered the cellular and molecular heterogeneity underlying the limited regenerative capacity of the neonatal mouse cochlea. Notch repression broadly silenced key SC genes, yet only a rare subpopulation of Deiters cells (DC), termed responsive DCs, initiated the trans-differentiation into HC fate. These cells underwent coordinated transcriptional and enhancer remodeling, linking epigenetic priming with morphological plasticity, while other SCs remained refractory despite robust Notch targets downregulation. Our study provides a molecular definition of a fate-primed SC state, revealing Notch inhibition as a selective trigger that unmasks rare regenerative competence.
2026-04-30 | GSE310785 | GEO
Project description:Regeneration enables organisms to repair damaged tissues, yet this capacity is strikingly limited in the cochlear sensory epithelium, essential for sound detection. A major cause of hearing loss arises from the irreversible loss of sensory hair cells (HCs) in the cochlea. While supporting cells (SCs) have a latent ability to trans-differentiate into HCs, this regenerative potential is rapidly lost after development. Using live imaging and single-cell multiomics of cochlear explants, we uncovered the cellular and molecular heterogeneity underlying the limited regenerative capacity of the neonatal mouse cochlea. Notch repression broadly silenced key SC genes, yet only a rare subpopulation of Deiters cells (DC), termed responsive DCs, initiated the trans-differentiation into HC fate. These cells underwent coordinated transcriptional and enhancer remodeling, linking epigenetic priming with morphological plasticity, while other SCs remained refractory despite robust Notch targets downregulation. Our study provides a molecular definition of a fate-primed SC state, revealing Notch inhibition as a selective trigger that unmasks rare regenerative competence.
2026-04-01 | GSE313875 | GEO