Islet Gene View—a tool to facilitate islet research-Reference-Cited by-同舟云学术

Islet Gene View—a tool to facilitate islet research

Published:2022-08-10 Issue:12 Volume:5 Page:e202201376
ISSN:2575-1077
Container-title:Life Science Alliance
language:en
Short-container-title:Life Sci. Alliance

Author:

Asplund Olof¹²^ORCID,Storm Petter¹²³,Chandra Vikash⁴^ORCID,Hatem Gad¹²,Ottosson-Laakso Emilia¹²,Mansour-Aly Dina¹²,Krus Ulrika¹²,Ibrahim Hazem⁴^ORCID,Ahlqvist Emma¹²,Tuomi Tiinamaija¹²⁵⁶^ORCID,Renström Erik¹²,Korsgren Olle⁷⁸,Wierup Nils¹²,Ibberson Mark⁹,Solimena Michele¹⁰¹¹¹²,Marchetti Piero¹³^ORCID,Wollheim Claes¹²¹⁴,Artner Isabella¹²,Mulder Hindrik¹²,Hansson Ola¹²⁶^ORCID,Otonkoski Timo⁴¹⁵^ORCID,Groop Leif¹²⁶,Prasad Rashmi B¹²⁶¹⁶^ORCID

Affiliation:

1. Department of Clinical Sciences, Clinical Research Centre, Lund University, Malmö, Sweden

2. Lund University Diabetes Centre (LUDC), Lund, Sweden

3. Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund, Sweden

4. Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland

5. Department of Endocrinology, Abdominal Centre, Helsinki University Hospital, Folkhalsan Research Center, Helsinki, Finland

6. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

7. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

8. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

9. Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland

10. Paul Langerhans Institute Dresden of the Helmholtz Center, Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Dresden, Germany

11. German Center for Diabetes Research (DZD), Munich, Germany

12. Max Planck Institute of Molecular Cell Biology and Genetics, (MPI-CBG), Dresden, Germany

13. Department of Clinical and Experimental Medicine, Cisanello, University Hospital, University of Pisa, Pisa, Italy

14. Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland

15. Children’s Hospital, Helsinki University Hospital, Helsinki, Finland

16. Human Tissue Laboratory at Lund University Diabetes Centre, Lund, Sweden

Abstract

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.

Funder

Swedish Research Council

Swedish Foundation for Strategic Research to the Lund University Diabetes Centre

JDRF

Diabetes Wellness

Regeneron and Eli Lilly

Innovative Medicines Initiative 2 Joint Undertaking

European Union’s Horizon 2020 Research and Innovation Programme and EFPIA

Swiss State Secretariat for Education‚ Research and Innovation

Crafoord Foundation

Heart Lung Foundation

Hjelt Foundation