TY - JOUR T1 - Islet Gene View - a tool to facilitate islet research JF - bioRxiv DO - 10.1101/435743 SP - 435743 AU - Olof Asplund AU - Petter Storm AU - Vikash Chandra AU - Emilia Ottosson-Laakso AU - Gad Hatem AU - Dina Mansour-Aly AU - Ulrika Krus AU - Hazem Ibrahim AU - Emma Ahlqvist AU - Tiinamaija Tuomi AU - Erik Renström AU - Olle Korsgren AU - Nils Wierup AU - Claes Wollheim AU - Isabella Artner AU - Hindrik Mulder AU - Ola Hansson AU - Timo Otonkoski AU - Leif Groop AU - Rashmi B Prasad AU - on behalf of the Human Tissue Laboratory at Lund University Diabetes Centre Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/16/435743.abstract N2 - Changes in the hormone-producing pancreatic islets are central culprits in type 2 diabetes (T2D) pathogenesis. Characterization of gene expression in islets how it is altered in T2D are therefore vital in understanding islet function and T2D pathogenesis. We leveraged RNA-sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. The IGW combines expression data for a given gene with phenotypical data such as T2D status, BMI, HbA1c, insulin secretion, purity of islets, etc.), regulation of gene expression by genetic variants e.g., expression quantitative trait loci (eQTLs) and relationship with expression of islet hormones. In IGW, 285 differentially expressed genes (DEGs) were identified in T2D donors islets compared to controls. Forty percent of the DEGs showed cell-type enrichment and a large proportion of them were significantly co-expressed with islet hormone-encoding genes like glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%) and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2 impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model.Significance Statement We present Islet Gene View (IGW), a web resource facilitating information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. In IGW, we explored RNA expression from 188 donor-islets and examined their relationship with islet phenotypes including insulin secretion and expression of genes encoding islet hormones. GWAS have shown 403 genetic variants associated with risk of type 2 diabetes (T2D) risk, however, the target genes and function of these variants in islets are largely unknown. By linking T2D risk variants to expression in islets from T2D and non-diabetic donors as well as islet phenotypes, use of IGW provided new insight into mechanisms by which variants in these loci may increase risk of T2D.Competing Interest StatementThe authors have declared no competing interest. ER -