Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of a novel isoform of Slc26a4 by single-cell RNA-sequencing of pendrin-expressing cells in the cochlea - Illumina

ABSTRACT: Pathogenic variation in the coding sequence of SLC26A4 causes both Pendred syndrome (PDS) and non-syndromic enlarged vestibular aqueduct (NSEVA/DFNB4), two autosomal recessive disorders. The former accounts for approximately 6% of human genetic hearing loss, making it the second most common form of syndromic deafness after Usher syndrome, while the latter is the most common radiological malformation associated with childhood sensorineural hearing loss (SNHL). Here, we used short- and long-read single-cell RNA sequencing (scRNA-seq) of pendrin-expressing cells in the murine cochlea to identify a novel short isoform of Slc26a4. We demonstrate that the short Slc26a4 isoform is expressed in both the inner ear and kidney and investigate its interactions and functions. We also characterize the genotype-phenotype association for SLC26A4-related hearing loss in the context of these two isoforms. These results provide a new reference for molecular profiling of pendrin and offer novel insights into cell-type-specific splicing events and SLC26A4-related hearing loss.

ORGANISM(S): Mus musculus

PROVIDER: GSE299255 | GEO | 2026/07/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of a novel isoform of Slc26a4 by single-cell RNA-sequencing of pendrin-expressing cells in the cochlea - Nanopore

Project description:Pathogenic variation in the coding sequence of SLC26A4 causes both Pendred syndrome (PDS) and non-syndromic enlarged vestibular aqueduct (NSEVA/DFNB4), two autosomal recessive disorders. The former accounts for approximately 6% of human genetic hearing loss, making it the second most common form of syndromic deafness after Usher syndrome, while the latter is the most common radiological malformation associated with childhood sensorineural hearing loss (SNHL). Here, we used short- and long-read single-cell RNA sequencing (scRNA-seq) of pendrin-expressing cells in the murine cochlea to identify a novel short isoform of Slc26a4. We demonstrate that the short Slc26a4 isoform is expressed in both the inner ear and kidney and investigate its interactions and functions. We also characterize the genotype-phenotype association for SLC26A4-related hearing loss in the context of these two isoforms. These results provide a new reference for molecular profiling of pendrin and offer novel insights into cell-type-specific splicing events and SLC26A4-related hearing loss.

2026-07-17 | GSE299257 | GEO

Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome

Project description:Enlarged vestibular aqueducts (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function.

2020-04-22 | PXD017011 | Pride

Transcription profiling of mouse stria vascularis from animals lacking Slc26a4 and heterzygous controls before the onset of hearing.

Project description:Determination of differential expression of genes in the stria vascularis of pendrin (Slc26a4) heterozygous and knockout mice before the onset of hearing at postnatal day 10 (P10). Experiment Overall Design: A total of Six samples of stria vascularis RNA obtained from P10 mice were analyzed. Triplicates from pendrin (Slc26a4) heterozygous and knockout mice were run and analyzed.

2009-03-01 | E-GEOD-10587 | biostudies-arrayexpress

Gene expression in stria vascularis of mice lacking Slc26a4 and heterzygous controls before the onset of hearing.

2009-02-19 | GSE10587 | GEO

Transcription profiling of mouse thyroid from Slc26a4 animals vs. heterzygous controls.

Project description:Determination of differential expression of genes in the thyroid of pendrin (Slc26a4) heterozygous and knockout mice at a time point corresponding to maximal thyroid gland activity, postnatal day 15 (P15). Experiment Overall Design: A total of Six samples of thyroid RNA obtained from P15 mice were analyzed. Triplicates from pendrin (Slc26a4) heterozygous and knockout mice were run and analyzed.

2009-03-01 | E-GEOD-10589 | biostudies-arrayexpress

Gene expression in the embryonic endolymphatic sac of E13.5, E14.5, E16.5 and E17.5 Slc26a4Δ/+ and Slc26a4Δ/Δ mice

Project description:Gene expression was analyzed in endolymphatic sacs of two groups of mice: Slc26a4Δ/Δ and Slc26a4Δ/+ mice. Slc26a4Δ/Δ mice fail to develop hearing and are a model for Enlarged Vestibular Aqueduct and Pendred Syndrome, two forms of human deafness that are associated with mutations of SLC26A4. Slc26a4Δ/+ mice develop normal hearing and served a controls. Gene expression was performed at embryonic day (E) 13.5, E14.5, E16.5 and E17.5, which are pathobiologically relevant time points that mark growth and enlargement of the entire inner ear including the cochlea and the vestibular aqueduct. Affymetrix microarrays were used to analyze gene expression and developmental changes in gene expression in Slc26a4Δ/Δ and Slc26a4Δ/+ mice with the goal to identify genes that are in a functional relationship with Slc26a4, the gene that codes for pendrin.

2017-09-22 | GSE90092 | GEO

Single-cell RNA-sequencing of stria vascularis cells in the adult Slc26a4-/- mouse

Project description:The primary pathological alternations of SLC26A4-related hearing loss are endolymphatic pH acidification and luminal enlargement of the inner ear. However, the molecular cell type-specific influences remain poorly characterized. In this study, we confirmed a method of isolating single cells in the cochlea's stria vascularis (SV) from wild-type (WT) animals. We then applied it to characterize the distinct transcriptomes from mutant (Slc26a4+/- and Slc26a4-/-) samples. Single-cell RNA-sequencing (scRNA-seq) identified transcriptional profiles in Slc26a4-expressing (spindle) cells and Kcnj10-expressing (intermediate) cells of the SV. By Gene Set Enrichment Analysis (GSEA), we found that spindle cells contain extrinsic cellular components, a factor that enables cell-to-cell communication. In addition, the gene expression profile informed signaling pathways associated with pH regulation in spindle cells. Compared to WT control, the transcriptional profiles in the SV cells of Slc26a4-/- mice showed downregulation of extracellular exosome-related genes in spindle cells and GPI-anchor-related genes in the intermediate cells. Immunofluorescence studies in spindle cells of Slc26a4-/- mice validated the increased expression of the clathrin-mediated endocytosis-related protein. Overall, cell isolation of SV from WT and mutant (Slc26a4+/- and Slc26a4-/-) samples combined with cell type-specific transcriptomic analyses revealed pH-dependent alternations in spindle cells and intermediate cells, inspiring further studies into the dysfunctional role of SV cells in SLC26A4-related hearing loss.

2023-03-14 | GSE221146 | GEO

Comparison of gene expression between the thyroid of mice lacking Slc26a4 and heterzygous controls.

2009-02-19 | GSE10589 | GEO

Functional significance of the SLC26A4 gene in silica-induced pulmonary toxicity

Project description:Previous studies in our laboratory identified a correlation between silica-induced pulmonary toxicity and SLC26A4 transcript levels in the lungs of rats. To determine the role of the SLC26A4 gene product, pendrin (Pds) in silica-induced pulmonary toxicity, pendrin wild type (WT) and knockout (KO) mice were employed. All mice were exposed to either air or crystalline silica (15 mg/m3, 6 hours/day, 4 days) and pulmonary toxicity and lung gene expression profiles determined at post-exposure time intervals of 1-day, 3-months, and 9-months. Silica exposure resulted in the induction of pulmonary toxicity in both the WT and KO mouse strains, compared to corresponding air exposed controls. However, there were significant differences (p<0.05) in the measured pulmonary toxicity parameters between silica exposed WT and KO groups being more severe in the WT compared with the KO mice. Significant differences in the gene expression profiles were also detected in the WT and KO mice in response to their exposure to crystalline silica.

2022-10-23 | GSE139287 | GEO