Gene expression during synaptic regeneration between cochlear hair cells and neurons
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ABSTRACT:
PROVIDER: PRJNA540476 | ENA |
REPOSITORIES: ENA
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Project description:Significant changes in the expression of synaptic and inflammatory genes were observed early after damage, during regeneration of the fibers and synapses, and after completion of in vitro regeneration between afferent neurons and cochlear hair cells.
2020-09-14 | GSE130495 | 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 hair cells. Hair cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which the endogenous Atoh1 gene was fused with GFP Two replicates of GFP+ hair cells were compared with all other cochlear cell types that were GFP-
2015-03-01 | E-GEOD-65633 | biostudies-arrayexpress
Project description:The aim of this study is to identify the gene targets of Chd7 (by RNA-seq) in spiral ganglia neurons and cochlear hair cells. mRNA profiles of FACS-sorted spiral ganglia neurons from 4-day old mice and cochlear hair cells from embryos af 16.5 days in controls, Chd7 heterozygous and Chd7 homozygous mutant animals were generated by paired-end sequencing, in triplicate, using Illumina HiSeq 4000. The sequence reads that passed quality filters were reads were aligned to mouse MM10 genome assembly using HiSAT2 (version 2.1.0) with the default parameters in Galaxy (version 2.1.0). To facilitate quantitative gene expression analysis, aligned reads for each sample were counted using featureCounts (version1.6.4). Differential gene expression analysis was performed using DESeq2 (version 2.11.40.6), applying parametric fit. qRT–PCR validation was performed using SYBR Green and gene specific primers. To identify differentially expressed genes, RPKM values of genes that are not normally expressed in E16.5 hair cells or P4 spiral ganglia neurons were removed from analysis. This resulted in 6910 transcripts for genes expressed in hair cells and 11293 genes expressed in neurons. A pairwise comparison between controls and homozygotes and controls and heterozygotes was performed. Significant thresholds were considered for transcripts with an adjusted p-value (FDR) of ≤0.05 and linear fold change of >2 in either direction. Altered expression of selected genes was confirmed with qRT–PCR as well as the encoded proteins by immunohistochemistry. Analysis of differentially expressed genes uncovered novel targets and potential mechanisms by which Chd7 controls the survival of these cells during normal hearing.
2021-11-10 | GSE163798 | GEO
Project description:Hair cells (HCs) within the inner ear cochlea are highly specialized mechano-sensory cells that enable us to detect sound. In humans and other mammals, HC loss is permanent and a leading cause of deafness. Recent studies in newborn mice revealed that supporting cells (SCs) have the capacity to form cochlear HCs, and that inhibition of Notch signaling dramatically increases the otherwise low rate of SC-to-HC conversion. It has been proposed that in the absence of HCs, the SC-specific Notch ligand Jagged1 (JAG1) mediates the HC-repressive role of Notch signaling. Here we show that conditional deletion of Jag1 at postnatal day2 (P2) increases the rate of HC formation/regeneration in cochlear tissue and organoids. However, Jag1 deficiency also reduces the expression of key progenitor and metabolic genes and attenuates PI3K-Akt-mTOR signaling in cochlear SCs and Kölliker’s cells and we show that Notch1 and Notch2 are critical for mediating these pro-growth functions of Jag1. Conversely, we show that increasing JAG1/Notch signaling enhances the mitotic capacity of cochlear SCs/ Kölliker’s cells. Finally, we show that JAG1 expression declines in SCs as they undergo maturation, and that stimulation of JAG1 signaling boosts the ability of maturing cochlear SCs to form HCs in an mTOR-dependent manner.
2025-06-21 | GSE266157 | GEO
Project description:Outer and inner hair cells in the cochlea are essential for hearing, but are vulnerable to damage by genetic mutations and environmental insults, resulting in irreversible sensorineural hearing loss. Investigating these processes requires access to large numbers of human cochlear hair cells and the ability to precisely control genetic, biochemical, and environmental conditions. We recently established a new organoid system that recapitulates human cochlear differentiation. However, maturation of cochlear organoid cultures is inefficient, requiring several months to express the mature outer hair cell marker Prestin. To efficiently obtain fully functional outer hair cells, we tested the effects of the thyroid hormone thyroxine on hair cell maturation in human cochlear organoids. Thyroxine supplementation significantly increased the percentages of Prestin-positive hair cells in an age-dependent manner. Additionally, transcriptomic analyses revealed upregulation of mature outer hair cell genes and downregulation of immature hair cell genes in thyroxine-treated hair cells. Furthermore, some of the treated hair cells exhibited electromotility, a functional hallmark of mature outer hair cells. These results suggest that thyroid hormones accelerate the maturation of hair cells in human cochlear organoids, thereby useful for establishing an improved in vitro model for pre-clinical investigation on sensorineural hearing loss.
2025-12-17 | GSE292457 | GEO
Project description:Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop a treatment for hearing loss. HC regeneration in adult cochlea relies on a two-phase process: 1) Reprogramming mature cochlear (SCs) to regain the properties of their younger selves; 2) Activating Atoh1, a gene responsible for HC fate-determining, in the reprogrammed adult SCs for HC regeneration. We have shown that, by transient co-activation of Myc and NICD (Notch1 intracellular domain), the adult mouse cochlea can be successfully reprogrammed to a relatively younger stage and regain progenitor capacity, with the regeneration of HCs following Atoh1 overexpression in vitro and in vivo. To identify molecules to reprogram mature cochlear SCs and HC regeneration, we utilized single-cell RNA sequencing and uncovered the pathways and their target genes underlying MYC/NICD-mediated reprogramming. We used an in-house adult cochlea explant culture system and carried out single-cell RNA sequencing to examine the gene expression profiles of cochlear explants from a transgenic mouse model, rtTa/tet-Myc/-tet-NICD, in response to Dox-induced MYC/NICD co-activation. We compared gene expression profiles between Atoh1 activation vs. MYC/NICD/Atoh1 co-activation.
2023-06-01 | GSE218325 | GEO
Project description:Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop a treatment for hearing loss. HC regeneration in adult cochlea relies on a two-phase process: 1) Reprogramming mature cochlear (SCs) to regain the properties of their younger selves; 2) Activating Atoh1, a gene responsible for HC fate-determining, in the reprogrammed adult SCs for HC regeneration. We have shown that, by transient co-activation of Myc and NICD (Notch1 intracellular domain), the adult mouse cochlea can be successfully reprogrammed to a relatively younger stage and regain progenitor capacity, with the regeneration of HCs following Atoh1 overexpression in vitro and in vivo. We identified a combination (the cocktail) of drug-like molecules composing of small molecules and siRNAs to activate the pathways of Myc, Notch1, Wnt and cAMP. To identify molecules to reprogram mature cochlear SCs and HC regeneration, we utilized single-cell RNA sequencing and uncovered the pathways and their target genes underlying chemical-mediated reprogramming. We used an in-house adult cochlea explant culture system and carried out single-cell RNA sequencing to examine the gene expression profiles of cochlear explants, in response to chemical-induced reprogramming. We compared gene expression profiles between Vehicle/ad.Atoh1 activation vs. Cocktail (chemical reprogramming)/ad.Atoh1 activation.
2023-06-01 | GSE218324 | GEO
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear hair cells. Hair cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which the endogenous Atoh1 gene was fused with GFP
2015-03-01 | GSE65633 | GEO
Project description:The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration
| PRJNA1106021 | ENA