RNAseq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE73060 |
| Title | RNAseq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells |
| Description | The specialized corneal epithelium requires differentiated properties, specific for its role at the anterior surface of the eye, thus tight maintenance of the differentiated qualities of the corneal epithelial is essential. Our studies have focused on pinin (PNN), an exon junction component (EJC) that has dramatic implications on corneal epithelial cell differentiation and may act as a stabilizer of the corneal epithelial cell phenotype. Our studies revealed that PNN is involved in both transcriptional repression complexes and the spliceosomal complexes, placing PNN at the fulcrum between chromatin and mRNA splicing. Transcriptome analysis of PNN-knockdown cells revealed clear and reproducible alterations in transcript profiles and splicing patterns of a subset of genes that would significantly impact the epithelial cell phenotype. Here, we further investigate PNNs role in the regulation of gene expression and alternative splicing (AS) in a corneal epithelial context. We used human corneal epithelial cells (HCET cells) that carry doxycycline-inducible PNN-knockdown shRNA vector and performed RNA-seq to determine differential gene expression and differential AS events. Multiple genes and AS events were identified as differentially expressed between PNN-knockdown and controls cells. Genes up-regulated by PNN-knockdown included a large proportion of genes that are associated with processes associated with enhanced cell migration and ECM remodeling including: MMPs, ADAMs, HAS2, LAMA3, CXCRs and UNC5C. Genes down-regulated in response to PNN depletion included: IGFBP5. FGD3, FGFR2, PAX6, RARG and SOX10. AS events in PNN compared to controls was also more likely to be detected, and uregulated in PNN-knockdowns. In particular, 60%% of exon skipping events detected in only one condition were detected in PNN-knockdowns and of the shared exon skipping events, 92%% of those differentially expressed were more frequent in the PNN-knockdown. This suggests that in the absence of PNN the epithelial cells are dramatically transformed in the amount and composition of isoforms and that PNN plays a crucial role in the selection of which isoforms differentiating cells produce. Many of the genes affected by PNN-knockdown are known to affect epithelial phenotype. This window into the complexity of RNA splicing in the corneal epithelium implies that PNN exerts broad influence over the regulation and maintenance of epithelial cell phenotype. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73060 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE41616
Identification of Novel Molecular Markers through Transcriptomic Analysis in Human Fetal and Adult Corneal Endothelial Cells
1
GSE59822
Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dy...
1
GSE64357
Knockout mice reveal an essential role for Epithelial splicing regulatory proteins (Esrps) in mammalian development and epithelial splicing in vivo
1
GSE65991
Transcriptomic analysis of cultured corneal endothelial cells as a validation for their use in cell-replacement therapy
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
