{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298461"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MEG3 Prevents Cell Death by Restoring Autophagic Flux in Developing Neurons with CLCN4 Variants","description":"Variations in CLCN4, encoding the H+/Cl- exchanger CLC-4, are associated with neurodevelopmental disorders, yet their mechanisms remain unclear. To investigate their impact, we introduced patient-relevant CLCN4 variants into human pluripotent stem cells via genome editing and differentiated them into neurons and brain organoids. CLCN4 variants led to a reduction in excitatory neurons due to early-stage neurodegeneration, altering vesicular dynamics in the endo-lysosomal system, disrupting autophagic flux, and increasing neuronal vulnerability. Transcriptomic profiling identified MEG3, a significantly downregulated long non-coding RNA in CLCN4-variant neurons. Restoring MEG3 expression rescued autophagic flux, mitigated lysosomal dysfunction, and improved survival of CLCN4-variant neurons. These findings establish a link between CLCN4 dysfunction, impaired autophagy, and neurodegeneration, highlighting MEG3 as a potential therapeutic target for neurodevelopmental disorders involving autophagy dysfunction.","dates":{"publication":"2026/05/29"},"accession":"GSE298461","cross_references":{"GSM":["GSM9014941","GSM9014940","GSM9014939","GSM9014938"],"GPL":["24676"],"GSE":["298461"],"taxon":["Homo sapiens"]}}