Islet Gene View-a tool to facilitate islet research.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
10 08 2022
10 08 2022
Historique:
received:
19
01
2022
revised:
18
07
2022
accepted:
18
07
2022
entrez:
10
8
2022
pubmed:
11
8
2022
medline:
13
8
2022
Statut:
epublish
Résumé
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 (<i>GCG</i>, 56%), amylin (<i>IAPP</i>, 52%), insulin (<i>INS</i>, 44%), and somatostatin (<i>SST</i>, 24%). Inhibition of two DEGs, <i>UNC5D</i> and <i>SERPINE2</i>, 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.
Identifiants
pubmed: 35948367
pii: 5/12/e202201376
doi: 10.26508/lsa.202201376
pmc: PMC9366203
pii:
doi:
Substances chimiques
Insulin
0
Serpin E2
0
Glucagon
9007-92-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 Asplund et al.
Références
Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13924-9
pubmed: 25201977
Ann N Y Acad Sci. 2006 Nov;1084:89-117
pubmed: 17151295
Transplantation. 2011 Mar 27;91(6):677-83
pubmed: 21248660
PLoS Genet. 2015 Dec 01;11(12):e1005694
pubmed: 26624892
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Diabetes. 2016 Aug;65(8):2311-21
pubmed: 27207556
Nat Methods. 2018 Jul;15(7):543-546
pubmed: 29915188
Nat Genet. 2018 Nov;50(11):1505-1513
pubmed: 30297969
Lancet Diabetes Endocrinol. 2018 May;6(5):361-369
pubmed: 29503172
Nat Rev Mol Cell Biol. 2007 Apr;8(4):296-306
pubmed: 17356579
Mol Cell Biol. 2003 Sep;23(17):6049-62
pubmed: 12917329
Cell Metab. 2016 Oct 11;24(4):593-607
pubmed: 27667667
PLoS One. 2017 Aug 28;12(8):e0182932
pubmed: 28846711
J Biol Chem. 2008 Apr 18;283(16):10264-75
pubmed: 18285336
J Clin Invest. 1980 Feb;65(2):233-41
pubmed: 6153182
Genes (Basel). 2015 Mar 12;6(1):87-123
pubmed: 25774817
Cell Death Dis. 2020 May 18;11(5):378
pubmed: 32424151
Nat Commun. 2020 Sep 30;11(1):4912
pubmed: 32999275
Diabetologia. 2019 Feb;62(2):286-291
pubmed: 30413829
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Diabetes. 2017 Nov;66(11):2888-2902
pubmed: 28566273
Diabetologia. 2015 Feb;58(2):221-32
pubmed: 25421524
Nat Genet. 2012 May 13;44(6):659-69
pubmed: 22581228
Hum Mol Genet. 2015 Apr 1;24(7):1945-55
pubmed: 25489054
Blood. 2012 Mar 15;119(11):2452-7
pubmed: 22234688
FEBS J. 2010 Mar;277(6):1410-9
pubmed: 20136655
N Engl J Med. 2008 Nov 20;359(21):2220-32
pubmed: 19020324
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
J Clin Invest. 2011 Sep;121(9):3589-97
pubmed: 21865645
PLoS Genet. 2014 Apr 03;10(4):e1004235
pubmed: 24699409
Diabetologia. 2018 Mar;61(3):641-657
pubmed: 29185012
Lancet Oncol. 2018 Dec;19(12):1590-1601
pubmed: 30416076
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2301-2306
pubmed: 28193859
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16480-5
pubmed: 24065825
Nat Biotechnol. 2007 Mar;25(3):309-16
pubmed: 17344885
Cell Rep. 2014 Dec 24;9(6):2206-18
pubmed: 25497100
Diabetologia. 2011 Apr;54(4):828-42
pubmed: 21212933
Genome Biol. 2009;10(9):239
pubmed: 19785719
Diabetes. 2017 Aug;66(8):2296-2309
pubmed: 28490609
BMC Syst Biol. 2010 Jun 04;4:78
pubmed: 20525321
Ups J Med Sci. 2016 May;121(2):81-95
pubmed: 27124642