Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distal Enhancer-Insulator Module of GDF6 is Essential for Cochlear Formation [single-cell multiome]

ABSTRACT: Mutations in approximately 30 genes have been linked to cochlear malformations, but the contribution of noncoding regulatory elements remains largely unclear. This study investigates the function of distal enhancer elements in the transcriptional regulation of GDF6, a gene implicated in cochlear development. Using mouse models with targeted deletions, human inner ear organoids, and CRISPR interference (CRISPRi), we identified a downstream regulatory interval harboring a developmental enhancer required to maintain GDF6 expression during otic epithelial maturation and cochlear morphogenesis. To characterize cellular composition and chromatin accessibility changes in patient (166-101) versus control (CA-26) iPSC-derived otic progenitor cells, we performed joint single-nucleus RNA-seq and ATAC-seq (10X Genomics Multiome) on CD271+ enriched populations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE331301 | GEO | 2026/06/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Distal Enhancer-Insulator Module of GDF6 is Essential for Cochlear Formation [ATAC-seq]

Project description:Inner-ear malformations cause congenital hearing loss, and several genes are known to guide inner-ear development. However, the contribution of noncoding regulatory elements remains largely unclear. This study investigates the function of distal enhancer elements in the transcriptional regulation of GDF6, a gene crucial for cochlear development. Using mouse models with targeted deletions, human iPSC-derived ear organoids (IEO), and CRISPR interference (CRISPRi) techniques, we identified a downstream regulatory interval harboring a developmental enhancer required to maintain GDF6 expression during otic epithelial maturation, vital for cochlear morphogenesis. Deletion of this regulatory region or targeting of CRISPRi-based repressors to these regions resulted in decreased GDF6 expression, failure of otic-epithelium development, and prevention of hair cell-like differentiation, reflecting cochlear aplasia observed in patients with corresponding genomic deletions. These findings highlight the essential role of long-range regulatory elements in auditory development and illustrate how their disruption contributes to human deafness.

2026-06-05 | GSE329998 | GEO

Distal Enhancer-Insulator Module of GDF6 is Essential for Cochlear Formation [ChIP-Seq]

2026-06-05 | GSE328473 | GEO

Derivation of cochlear organoids from human pluripotent stem cells reveals tight transcriptome-structure coupling during organogenesis

Project description:A balance of morphogen gradients during embryogenesis is thought to determine the identity of inner ear end organs. We applied this developmental principle to aggregates of human pluripotent stem cells and found that modulations of Sonic Hedgehog and WNT signaling promote stem cell-derived otic progenitors to express ventral otic markers. Strikingly, these ventralized otic progenitors gave rise to hair cells with short hair bundles comprised of stereocilia arrayed in a geometry reminiscent of cochlear hair cells. Moreover, these ventralized hair cells expressed multiple markers defining outer or inner hair cells in the cochlea. These results reveal that early morphogenic signals are sufficient for not only establishing cochlear gene expression, but also defining structural properties pertaining to the cochlear sensory epithelium.

2022-04-14 | GSE200629 | GEO

Gene expression profiles at the single cell level of cochlear cells from C57BL/6J mice at both embryonic day 15 and postnatal day 7

Project description:Otic Mesenchyme Cells (OMCs) are the numerous cell type during cochlear development. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of OMCs during cochlear development

2023-05-18 | GSE217727 | GEO

Distal Enhancer-Insulator Module of GDF6 is Essential for Cochlear Formation

Project description:This SuperSeries is composed of the SubSeries listed below.

2026-06-05 | GSE329999 | GEO

Quantitative Proteomics of Cochlear Tissues: Bilateral Comparisons in Guinea Pigs and Rats

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

Rat Normal Cochlear Nucleus

Project description:The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. It is heterogeneous in neuronal populations and physiologic responses and is organized in three major subdivisions: the anterior ventral cochlear nucleus (AVCN), the posterior ventral cochlear nucleus (PVCN) and the dorsal cochlear nucleus (DCN). Although each region demonstrates multiple cell types and functions, there are predominant populations of neurons in each region that underlie the principal role each subdivision plays in auditory processing. Little is known of the underlying genetic contribution to these properties. This study sought to identify genes expressed in the subdivisions of the cochlear nucleus that may account for the anatomical and physiological characteristics of each subdivision. These data provide a genetic basis for understanding normal auditory processing in the cochlear nucleus and a template for investigating changes that may occur with hearing loss, the generation and percept of tinnitus, and central processing disorders. Keywords: normal, comparative Brown Norway rats (n=40, female, 45days) were anesthetized and decapitated. Brains were rapidly removed and the subdivisions of the cochlear nucleus (AVCN, PVCN and DCN) dissected on dry ice. Total RNA was extracted and tested for concentration and purity by spectrophotometry and integrity by gel electrophoresis. SAGE was performed using the NlaIII enzyme and Invitrogen SAGE kit. Concatemers were commercially sequenced and imported into eSAGE (Margulies and Innis, 2000) for tag extraction and frequency.

2005-12-31 | E-GEOD-3628 | biostudies-arrayexpress

Unraveling the Molecular Landscape of Lead-Induced Cochlear Synaptopathy: A Quantitative Proteomic Analysis

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

Transcriptomic profiling reveals key early response genes during GDF6-mediated differentiation of human adipose-derived stem cells to nucleus pulposus cells

Project description:Stem cell-based therapies show promise as a means of repairing the degenerate intervertebral disc, with growth factors often used alongside cells to help direct differentiation towards a nucleus pulposus (NP)-like phenotype. We previously demonstrated adipose-derived stem cell (ASCs) differentiation with GDF6 as optimal for generating NP-like cells through evaluating end-stage differentiation parameters. Here we conducted a time-resolved transcriptomic characterisation of ASCs response to GDF6 stimulation to understand the early drivers of differentiation to NP-like cells.

2025-03-26 | E-MTAB-13435 | biostudies-arrayexpress

Rat Normal Cochlear Nucleus

2006-01-01 | GSE3628 | GEO