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1 型糖尿病患者内分泌胰腺和免疫系统的多重原位成像质谱细胞术分析。

Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes.

机构信息

Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Medical Research, Corporal Michael J. Crescenz Veterans Affairs Medical Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Cell Metab. 2019 Mar 5;29(3):769-783.e4. doi: 10.1016/j.cmet.2019.01.003. Epub 2019 Jan 31.

Abstract

The interaction between the immune system and endocrine cells in the pancreas is crucial for the initiation and progression of type 1 diabetes (T1D). Imaging mass cytometry (IMC) enables multiplexed assessment of the abundance and localization of more than 30 proteins on the same tissue section at 1-μm resolution. Herein, we have developed a panel of 33 antibodies that allows for the quantification of key cell types including pancreatic exocrine cells, islet cells, immune cells, and stromal components. We employed this panel to analyze 12 pancreata obtained from donors with clinically diagnosed T1D and 6 pancreata from non-diabetic controls. In the pancreata from donors with T1D, we simultaneously visualized significant alterations in islet architecture, endocrine cell composition, and immune cell presentation. Indeed, we demonstrate the utility of IMC to investigate complex events on the cellular level that will provide new insights on the pathophysiology of T1D.

摘要

免疫系统和胰腺内分泌细胞之间的相互作用对于 1 型糖尿病(T1D)的发生和进展至关重要。成像质谱细胞术(IMC)能够在 1μm 的分辨率下对同一切片上超过 30 种蛋白质的丰度和定位进行多重评估。在此,我们开发了一个 33 种抗体的面板,可用于定量分析包括胰腺外分泌细胞、胰岛细胞、免疫细胞和基质成分在内的关键细胞类型。我们使用该面板分析了 12 例来自临床诊断为 T1D 的供体的胰腺和 6 例来自非糖尿病对照者的胰腺。在来自 T1D 供体的胰腺中,我们同时可视化了胰岛结构、内分泌细胞组成和免疫细胞呈现的显著变化。事实上,我们证明了 IMC 可用于研究细胞水平上的复杂事件,这将为 T1D 的病理生理学提供新的见解。

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