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胰岛基因观察——一种有助于胰岛研究的工具。

Islet Gene View-a tool to facilitate islet research.

机构信息

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

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

出版信息

Life Sci Alliance. 2022 Aug 10;5(12):e202201376. doi: 10.26508/lsa.202201376.

DOI:10.26508/lsa.202201376
PMID:35948367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9366203/
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 (<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.

摘要

鉴定胰岛中的基因表达及其在 2 型糖尿病（T2D）中的改变对于理解胰岛功能和 T2D 发病机制至关重要。我们利用 RNA 测序和来自 188 位供体的胰岛全基因组基因分型，创建了胰岛基因观察（IGW）平台，以便科学界能够轻松获取这些信息。表达数据与胰岛表型、糖尿病状态、其他胰岛表达基因、胰岛激素编码基因以及胰岛素靶组织中的表达相关联。IGW 网络应用程序为特定感兴趣的基因生成输出图形。在 IGW 中，与对照相比，在 T2D 供体胰岛中鉴定出 284 个差异表达基因（DEGs）。40%的 DEGs 显示出细胞类型富集，并且很大一部分与胰岛激素编码基因显著共表达；胰高血糖素（<i>GCG</i>，56%）、胰岛素原（<i>IAPP</i>，52%）、胰岛素（<i>INS</i>，44%）和生长抑素（<i>SST</i>，24%）。抑制两个 DEGs，<i>UNC5D</i>和 <i>SERPINE2</i>，会损害葡萄糖刺激的胰岛素分泌，并影响人β细胞模型中的细胞存活。IGW 的探索性使用可以帮助设计更全面的功能后续研究，并有助于确定 T2D 的治疗靶点。

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