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Series GSE98485 Query DataSets for GSE98485
Status Public on Feb 02, 2018
Title A SRp55-regulated alternative splicing network controls pancreatic beta cell survival and function
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
Overall design Five independent preparations of EndoC-βH1 cells exposed to control (siCTL) or SRp55 (siSR#2) siRNAs
Contributor(s) Mateu JJ, Alvelos MI, Turatsinze J, Eizirik DL
Citation(s) 29246973, 33376132
Submission date May 02, 2017
Last update date Jul 25, 2021
Contact name Jonas Juan Mateu
Phone 003225556107
Organization name Universite Libre de Bruxelles
Department Faculty of Medecine
Lab ULB Center for Diabetes Research
Street address Route de Lennik 808 CP 618
City Brussels
ZIP/Postal code 1070
Country Belgium
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (10)
GSM2597305 control siRNA exposed 1
GSM2597306 control siRNA exposed 2
GSM2597307 control siRNA exposed 3
BioProject PRJNA385196
SRA SRP106195

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Supplementary file Size Download File type/resource
GSE98485_RAW.tar 42.4 Mb (http)(custom) TAR (of GTF)
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Raw data are available in SRA
Processed data provided as supplementary file

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