Transcriptional responses of human insulinoma cells to acute cytokine exposure

Purpose: The goal of this study is to characterize the effects of acute cytokine stimulations on human insulinoma cells, EndoC-betaH1, at the transcriptome level. Methods: mRNA profiles of EndoC-betaH1 cells with or without cytokine exposure were generated by deep sequencing, using Illumina Illumina HiSeq 2500. Results: Using an optimized data analysis workflow, we mapped about 100 million (2x100bp) paired reads per sample to the human genome (build hg38) and identified about 44,000 transcripts per sample with Star/Class workflow. Approximately 600 known genes showed differential expression between the Control and Cytokines, with a log fold change =1.5, at least one of the FPKM >=2 and p-value <0.05. Conclusions: Cytokine exposure did not alter the overall transcriptome profile. All three branches of the unfold protein response (UPR) were engaged in cytokine stress with upregulations of ER chaperones, protein disulfide isomerase and key transcription factors involved in adaptive UPR signaling. Key components of the apoptotic program were largely unchanged or modestly upregulated. In contrast, genes in the ER-associated protein degradation (ERAD) pathway were sharply activated. These findings provide a framework for comparative investigations of cytokine-induced differential protein expression by quantitative proteomics. Overall design: mRNA profiles of EndoC-betaH1 cells were generated by deep sequencing, using Illumina Illumina HiSeq 2500.