GSE98485: A SRp55-regulated alternative splicing network controls pancreatic beta cell survival and function

Gene Expression Data Explorer
Info Gene counts are sourced from ARCHS4, which provides uniform alignment of GEO samples. You can learn more about ARCHS4 and its pipeline here.
Enter gene symbol:

Select conditions below to toggle them from the plot:

GROUP CONDITION SAMPLES
EndoC-beta H1 human cell line
GSM2597310 GSM2597311 GSM2597312 GSM2597313 GSM2597314
GSM2597305 GSM2597306 GSM2597307 GSM2597308 GSM2597309
Description

Submission Date: May 02, 2017

Summary: Progressive failure of insulin-producing beta cells is the central event leading to diabetes, yet the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes.

GEO Accession ID: GSE98485

PMID: 29246973

Description

Submission Date: May 02, 2017

Summary: Progressive failure of insulin-producing beta cells is the central event leading to diabetes, yet the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes.

GEO Accession ID: GSE98485

PMID: 29246973

Visualize Samples

Info Visualizations are precomputed using the Python package scanpy on the top 5000 most variable genes.

Precomputed Differential Gene Expression

Info Differential expression signatures are automatically computed using the limma R package. More options for differential expression are available to compute below.

Signatures:

Select conditions:

Control Condition

Perturbation Condition

Only conditions with at least 1 replicate are available to select

Differential Gene Expression Analysis
Info Differential expression signatures can be computed using DESeq2 or characteristic direction.
Select differential expression analysis method:
Bulk RNA-seq Appyter

This pipeline enables you to analyze and visualize your bulk RNA sequencing datasets with an array of downstream analysis and visualization tools. The pipeline includes: PCA analysis, Clustergrammer interactive heatmap, library size analysis, differential gene expression analysis, enrichment analysis, and L1000 small molecule search.