Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing
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ABSTRACT:
PROVIDER: PRJNA464433 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The GJB6 gene is located just 35 kb telomeric to GJB2 in the so-called nonsyndromic hearing loss and deafness locus 1 (DFNB1). Knock out mouse models confirmed that inner ear expression of their protein products, connexin 30 (Cx30) and connexin 26 (Cx26), is crucial for hearing acquisition and normal development of the organ of Corti, however the coordinated regulation mechanism of Cx26 and Cx30 expression in the cochlea remains unclear. To investigate the mechanism underlying the etiopathogenesis of DFNB1, we used a microRNA (miRNA) and mRNA integrated expression profiling analysis on Cx30 -/- mice, which represent a model for humans in which large deletions in the DFNB1 locus lead to the down-regulation of both connexins and profound deafness.
2020-12-29 | GSE151368 | GEO
Project description:The GJB6 gene is located just 35 kb telomeric to GJB2 in the so-called nonsyndromic hearing loss and deafness locus 1 (DFNB1). Knock out mouse models confirmed that inner ear expression of their protein products, connexin 30 (Cx30) and connexin 26 (Cx26), is crucial for hearing acquisition and normal development of the organ of Corti, however the coordinated regulation mechanism of Cx26 and Cx30 expression in the cochlea remains unclear. To investigate the mechanism underlying the etiopathogenesis of DFNB1, we used a microRNA (miRNA) and mRNA integrated expression profiling analysis on Cx30 -/- mice, which represent a model for humans in which large deletions in the DFNB1 locus lead to the down-regulation of both connexins and profound deafness.
2020-12-29 | GSE151367 | GEO
Project description:The goal of this study was to isolate individual cochlear hair cells and supporting cells from wild type animals in order to characterize the transcriptome of functionally mature auditory hair cells in the mammalian cochlea.
2019-03-12 | GSE114157 | GEO
Project description: Not available
| S-EPMC6424336 | biostudies-literature
Project description:The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is downregulated predominantly by transcriptional silencing. Here we report that post-transcriptional inactivation of REST by alternative splicing is required for hearing in humans and mice. We show that in the mechanosensory hair cells of the mouse ear, regulated alternative splicing of a frameshift-causing exon into the Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous deletion of this alternative exon of mouse Rest causes hair cell degeneration and deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these mice. In humans, inhibition of the frameshifting splicing event by a novel REST variant is associated with dominantly inherited deafness. Our data reveal the necessity for alternative splicing-dependent regulation of REST in hair cells, and identify a potential treatment for a group of hereditary deafness cases.
2018-06-28 | GSE111604 | GEO
Project description:The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is downregulated predominantly by transcriptional silencing. Here we report that post-transcriptional inactivation of REST by alternative splicing is required for hearing in humans and mice. We show that in the mechanosensory hair cells of the mouse ear, regulated alternative splicing of a frameshift-causing exon into the Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous deletion of this alternative exon of mouse Rest causes hair cell degeneration and deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these mice. In humans, inhibition of the frameshifting splicing event by a novel REST variant is associated with dominantly inherited deafness. Our data reveal the necessity for alternative splicing-dependent regulation of REST in hair cells, and identify a potential treatment for a group of hereditary deafness cases.
2018-06-28 | GSE111602 | GEO
Project description:Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous-lethal of Gjb2 mutation in mice, there are currently no perfect mouse models carrying Gjb2 mutation to mimic human hereditary deafness and unveil the pathogenesis. Here, we first constructed heterozygous mutant mice, Gjb2+/35delG and Gjb2+/235delC, through androgenic haploid embryonic stem cells (AG-haESCs) mediated semi-cloning technology, which showed normal hearing function at P28. Furthermore, a homozygous mutant mouse model, Gjb235delG/35delG, was generated via enhanced tetraploid embryo complementation, which exhibited profound hearing loss like human patients at P14. Mechanism analysis showed that Gjb2 35delG disrupts the formation of intercellular gap junction channel and tunnel of Corti, and hair cell mechanotransduction, rather than the development of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism and opens up a new avenue for investigating the treatment for DFNB1A-related hereditary deafness.
2023-05-12 | GSE215106 | GEO
Project description:The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is downregulated predominantly by transcriptional silencing. Here we report that post-transcriptional inactivation of REST by alternative splicing is required for hearing in humans and mice. We show that in the mechanosensory hair cells of the mouse ear, regulated alternative splicing of a frameshift-causing exon into the Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous deletion of this alternative exon of mouse Rest causes hair cell degeneration and deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these mice. In humans, inhibition of the frameshifting splicing event by a novel REST variant is associated with dominantly inherited deafness. Our data reveal the necessity for alternative splicing-dependent regulation of REST in hair cells, and identify a potential treatment for a group of hereditary deafness cases.
2018-06-28 | GSE111603 | GEO
Project description:New Insights Into VDR Signaling In Mouse Intestinal Biology
| PRJNA553195 | ENA
Project description:To investigate the participation of deafness genes in the genetic program of the superior olivary complex (SOC), a prominent auditory brainstem center, we performed a comparative genome-wide microarray based gene expression analysis of the rat SOC and the rat brain at postnatal days (P) P4 and P25. Data were validated by qRT-PCR. Statistical analyses revealed 912 oligos up-regulated in the SOC at P4 and 1609 at P25. A total of 453 oligos were up-regulated in the SOC at both developmental stages. Subsequently, a list of 138 transcripts associated with hearing-impairment was extracted from publically available databases and literature. 26 of these transcripts were present in SOC-related gene signature lists, whereas only 11 were present in brain-related gene signature lists. Furthermore, in all 3 SOC-related gene signature lists, transcripts associated with hearing impairment were significantly enriched. Finally, there was a tendency of the SOC-related genes to map to human deafness loci with unknown etiology. Altogether, our study identified a tight genetic link between the SOC-related genetic program and deafness genes. The genome wide expression during the postnatal development of the SOC and the brain was investigated at two different time points: at postnatal (P) day 4 (before hearing onset) and at P25 (after hearing onset). Samples were hybridized onto two color platforms. At least 6 up to nine biological replicates per sample were performed.
2013-07-31 | E-GEOD-16764 | biostudies-arrayexpress