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

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

Author information

1
Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
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.
3
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Human Pancreas Analysis Program, https://hpap.pmacs.upenn.edu/.
5
Departments of Pathology and Pediatrics, University of Florida Diabetes Institute, Gainesville, FL 32610, USA.
6
Department of Medicine, Department of Molecular Physiology and Biophysics, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center VA, Tennessee Valley Healthcare, Nashville, TN, USA.
7
Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: kaestner@pennmedicine.upenn.edu.

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.

KEYWORDS:

T1D; histopathology; human pancreas; imaging; imaging mass cytometry; immune cell composition; immunolabeling; islet structure; multiplexed imaging; spatial information; type 1 diabetes

PMID:
30713110
PMCID:
PMC6436557
[Available on 2020-03-05]
DOI:
10.1016/j.cmet.2019.01.003

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