← BioTransfer GEO Dataset Finder
GEO series

MEG3 Prevents Cell Death by Restoring Autophagic Flux in Developing Neurons with CLCN4 Variants

GSE298461 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2026/05/29 Platform GPL24676
Summary
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.
This dataset
Download

Direct links to NCBI, no account and no request form: the whole study as GSE298461_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1269493 and SRA study SRP588584. Searching any of these in the dataset finder brings you back here.

Samples in this study

The sample list for this study is not cached yet. Press Sort into groups and it will be fetched from NCBI.

+ 4 more — browse all 4 samples with per-sample file links →

Similar datasets

Search all human RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.