{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328473/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328473"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Distal Enhancer-Insulator Module of GDF6 is Essential for Cochlear Formation [ChIP-Seq]","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.","dates":{"publication":"2026/06/05"},"accession":"GSE328473","cross_references":{"GSM":["GSM9684139","GSM9684138","GSM9684137","GSM9684136","GSM9684135","GSM9684134","GSM9684133","GSM9684132","GSM9684131","GSM9684130"],"GPL":["34281"],"GSE":["328473"],"taxon":["Homo sapiens"],"PMID":["[42313493]"]}}