Gene expression during synaptic regeneration between cochlear hair cells and neurons
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ABSTRACT:
PROVIDER: PRJNA540476 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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:Transcriptomes of control and Chd7-deficient spiral ganglia neurons and cochlear hair cells
| PRJNA687552 | ENA
Project description:Transcriptional profiling of cochlear neurons
| PRJNA472578 | ENA
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