TY - JOUR
T1 - Islet Gene View-a tool to facilitate islet research
AU - Asplund, Olof
AU - Storm, Petter
AU - Chandra, Vikash
AU - Hatem, Gad
AU - Ottosson-Laakso, Emilia
AU - Mansour-Aly, Dina
AU - Krus, Ulrika
AU - Ibrahim, Hazem
AU - Ahlqvist, Emma
AU - Tuomi, Tiinamaija
AU - Renström, Erik
AU - Korsgren, Olle
AU - Wierup, Nils
AU - Ibberson, Mark
AU - Solimena, Michele
AU - Marchetti, Piero
AU - Wollheim, Claes
AU - Artner, Isabella
AU - Mulder, Hindrik
AU - Hansson, Ola
AU - Otonkoski, Timo
AU - Groop, Leif
AU - Prasad, Rashmi B
N1 - © 2022 Asplund et al.
PY - 2022
Y1 - 2022
N2 - 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, UNC5D and SERPINE2, 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.
AB - 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, UNC5D and SERPINE2, 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.
U2 - 10.26508/lsa.202201376
DO - 10.26508/lsa.202201376
M3 - Article
C2 - 35948367
SN - 2575-1077
VL - 5
JO - Life Science Alliance
JF - Life Science Alliance
IS - 12
M1 - e202201376
ER -