Islet Gene View-a tool to facilitate islet research

Autor: Olof Asplund, Petter Storm, Vikash Chandra, Gad Hatem, Emilia Ottosson-Laakso, Dina Mansour-Aly, Ulrika Krus, Hazem Ibrahim, Emma Ahlqvist, Tiinamaija Tuomi, Erik Renström, Olle Korsgren, Nils Wierup, Mark Ibberson, Michele Solimena, Piero Marchetti, Claes Wollheim, Isabella Artner, Hindrik Mulder, Ola Hansson, Timo Otonkoski, Leif Groop, Rashmi B Prasad
Přispěvatelé: Research Programs Unit, University of Helsinki, STEMM - Stem Cells and Metabolism Research Program, Centre of Excellence in Stem Cell Metabolism, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Tiinamaija Tuomi Research Group, Clinicum, Department of Medicine, Helsinki University Hospital Area, Endokrinologian yksikkö, Helsinki One Health (HOH), HUS Children and Adolescents, Timo Pyry Juhani Otonkoski / Principal Investigator, Children's Hospital, Leif Groop Research Group, Departments of Faculty of Veterinary Medicine
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Life Sci. All. 5:e202201376 (2022)
Popis: Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are 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. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs,UNC5DandSERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human β-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.
Databáze: OpenAIRE