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通过多维胰腺表型分析了解 2 型糖尿病中的胰岛功能障碍:人类胰腺分析计划。

Understanding islet dysfunction in type 2 diabetes through multidimensional pancreatic phenotyping: The Human Pancreas Analysis Program.

机构信息

Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA; The Human Pancreas Analysis Program (RRID: SCR_016202).

Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Human Pancreas Analysis Program (RRID: SCR_016202).

出版信息

Cell Metab. 2022 Dec 6;34(12):1906-1913. doi: 10.1016/j.cmet.2022.09.013. Epub 2022 Oct 6.

DOI:10.1016/j.cmet.2022.09.013
PMID:36206763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9742126/
Abstract

In this perspective, we provide an overview of a recently established National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) initiative, the Human Pancreas Analysis Program for Type 2 Diabetes (HPAP-T2D). This program is designed to define the molecular pathogenesis of islet dysfunction by studying human pancreatic tissue samples from organ donors with T2D. HPAP-T2D generates detailed datasets of physiological, histological, transcriptomic, epigenomic, and genomic information. Importantly, all data collected, generated, and analyzed by HPAP-T2D are made immediately and freely available through a centralized database, PANC-DB, thus providing a comprehensive data resource for the diabetes research community.

摘要

在这个视角下,我们提供了一个最近成立的美国国立糖尿病、消化和肾脏疾病研究所(NIDDK)计划的概述,即 2 型糖尿病人类胰腺分析计划(HPAP-T2D)。该计划旨在通过研究患有 2 型糖尿病的器官捐献者的胰腺组织样本,来定义胰岛功能障碍的分子发病机制。HPAP-T2D 生成了详细的生理、组织学、转录组学、表观基因组学和基因组学信息数据集。重要的是,HPAP-T2D 收集、生成和分析的所有数据都通过一个集中的数据库 PANC-DB 立即免费提供,从而为糖尿病研究界提供了一个全面的数据资源。

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本文引用的文献

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Every islet matters: improving the impact of human islet research.每个胰岛都很重要:提高人类胰岛研究的影响力。
Nat Metab. 2022 Aug;4(8):970-977. doi: 10.1038/s42255-022-00607-8. Epub 2022 Aug 11.
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Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes.单细胞多组学分析人类胰岛揭示 1 型糖尿病中的新型细胞状态。
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Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state.
β细胞在整个生命周期和疾病中的表观遗传适应性:2型糖尿病中与年龄相关的去甲基化进程加快。
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Closing the Gap Between Vision and Victory in Type 1 Diabetes: The NIDDK Human Islet Research Network (HIRN) Initiative.缩小1型糖尿病领域愿景与胜利之间的差距:美国国立糖尿病、消化和肾脏疾病研究所人类胰岛研究网络(HIRN)倡议
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Accelerating Medicines Partnership in Type 2 Diabetes and Common Metabolic Diseases: Collaborating to Maximize the Value of Genetic and Genomic Data.2型糖尿病和常见代谢疾病加速药物合作组织:携手合作以最大化遗传和基因组数据的价值。
Diabetes. 2025 Jul 1;74(7):1089-1098. doi: 10.2337/db25-0042.
7
SEL1L-HRD1 ER-Associated Degradation Facilitates Prohormone Convertase 2 Maturation and Glucagon Production in Islet α Cells.SEL1L-HRD1内质网相关降解促进胰岛α细胞中激素原转化酶2的成熟和胰高血糖素的产生。
bioRxiv. 2025 Mar 20:2025.03.20.644437. doi: 10.1101/2025.03.20.644437.
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IFN-α Induces Heterogenous ROS Production in Human β-Cells.干扰素-α诱导人β细胞产生异质性活性氧。
bioRxiv. 2025 Feb 20:2025.02.19.639120. doi: 10.1101/2025.02.19.639120.
9
TMEM55A-mediated PI5P signaling regulates α-cell actin depolymerization and glucagon secretion.跨膜蛋白55A(TMEM55A)介导的磷脂酰肌醇5-磷酸(PI5P)信号传导调节α细胞肌动蛋白解聚和胰高血糖素分泌。
bioRxiv. 2024 Dec 17:2024.12.16.628242. doi: 10.1101/2024.12.16.628242.
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G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.G6PC2 通过确定胰腺α细胞中葡萄糖的设定点来控制胰高血糖素的分泌。
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2 型糖尿病中 α 细胞功能的异质性损伤与细胞成熟状态有关。
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Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry.使用多光谱成像质谱流式细胞术分析 2 型糖尿病患者的人胰腺单细胞。
Cell Rep. 2021 Nov 2;37(5):109919. doi: 10.1016/j.celrep.2021.109919.
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TIGER: The gene expression regulatory variation landscape of human pancreatic islets.TIGER:人类胰岛的基因表达调控变异景观。
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Nat Metab. 2021 Jul;3(7):894-895. doi: 10.1038/s42255-021-00415-6.
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Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes.对活体人胰腺胰岛供体的多组学分析揭示了 2 型糖尿病β细胞向不同方向发展的轨迹。
Nat Metab. 2021 Jul;3(7):1017-1031. doi: 10.1038/s42255-021-00420-9. Epub 2021 Jun 28.
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Pancreatlas: Applying an Adaptable Framework to Map the Human Pancreas in Health and Disease.胰腺图谱:应用适应性框架绘制健康与疾病状态下的人类胰腺图谱。
Patterns (N Y). 2020 Oct 5;1(8):100120. doi: 10.1016/j.patter.2020.100120. eCollection 2020 Nov 13.
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The evolving metabolic landscape of chromatin biology and epigenetics.染色质生物学和表观遗传学的不断变化的代谢景观。
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Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D.人类胰岛发生的单细胞转录组学定义了 T2D 中β细胞去分化的分子基础。
Mol Metab. 2020 Dec;42:101057. doi: 10.1016/j.molmet.2020.101057. Epub 2020 Jul 30.