← BioTransfer GEO Dataset Finder
GEO series

Influence of the WDR4 c.251G>A (p.R84H) variant on the transcriptome in human fibroblasts

GSE242969 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/10/08 Platform GPL24676
Summary
The WD repeat-containing protein 4 (WDR4) has repeatedly been associated with primary microcephaly, a condition of impaired brain and skull growth, which may be due to faulty cilia. Here, we show using a combination of approaches in human fibroblasts, zebrafish embryos and patient-derived cells that WDR4 facilitates cilium formation. Molecularly, we associated WDR4 loss-of-function with increased protein synthesis and concomitant upregulation of proteasomal activity, while ubiquitin precursor pools are reduced. Inhibition of proteasomal activity as well as supplementation with free ubiquitin restored normal ciliogenesis. Proteasome inhibition ameliorated microcephaly phenotypes. Thus, we propose that WDR4 loss-of-function impairs head growth and neurogenesis via aberrant cilia formation, initially caused by disturbed protein and ubiquitin homeostasis.
Published in
Cilia defects upon loss of WDR4 are linked to proteasomal hyperactivity and ubiquitin shortage
Burkhalter MD, Stiff T, Maerz LD et al. · Cell death & disease 2024 · PMID 39251572 · doi:10.1038/s41419-024-07042-5
This dataset
Download

Direct links to NCBI, no account and no request form: the whole study as GSE242969_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1015637 and SRA study SRP459953. 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.

+ 8 more — browse all 8 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.