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

Cell metabolism | 2019

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.

Pubmed ID: 30713110 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK104211
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK112232
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020593
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK104119
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK112217
  • Agency: NIDDK NIH HHS, United States
    Id: UC4 DK108132
  • Agency: NIDDK NIH HHS, United States
    Id: R24 DK106755
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK019525

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This is a list of tools and resources that we have found mentioned in this publication.


R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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CellProfiler Image Analysis Software (tool)

RRID:SCR_007358

Software tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.

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Cytobank (tool)

RRID:SCR_014043

A cloud-based platform which allows users to analyze, visualize, and archive multiparamter cytometry data for single-cell biology. Multiple single-cell data sets can be analyzed and visualized simultaneously with a variety of graphics, inlcuding Sunburst, SPADE, and viSNE. Users can store and back up related data such as protocols, microscopy images, and presentations and collaborate and share analysis and data sets with other Cytobank users. Cytobank also provides a variety of services and training sessions to assist with experiment workflow.

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Network for Pancreatic Organ Donors with Diabetes (tool)

RRID:SCR_014641

A collaborative research project that supports nPOD approved diabetes investigators by freely providing rare and difficult-to-obtain tissues from type 1 and type 2 diabetes donors. Interested researchers are encouraged to apply to obtain nPOD tissues, or to request access to analyze cases in the nPOD Online Pathology site. Interested donors can contact nPOD directly for more information.

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Anti-ghrelin (C-18) Antibody (antibody)

RRID:AB_2232479

This polyclonal targets GHRL

View all literature mentions

Pancreatic Polypeptide antibody (antibody)

RRID:AB_1524152

This polyclonal targets Human Pancreatic Polypeptide

View all literature mentions

HLA DR antibody [TAL 1B5] (antibody)

RRID:AB_445401

This monoclonal targets HLA DR antibody [TAL 1B5]

View all literature mentions

Anti-NKX6-1 polyclonal antibody (antibody)

RRID:AB_10673664

This polyclonal targets NKX6-1

View all literature mentions

NCAM1/CD56 antibody (antibody)

RRID:AB_2149421

This polyclonal targets NCAM1/CD56

View all literature mentions

Anti- Somatostatin (H-106) Antibody (antibody)

RRID:AB_2195930

This polyclonal targets Somatostatin

View all literature mentions

Human PDX-1/IPF1 Affinity Purified Polyclonal Ab (antibody)

RRID:AB_355257

This polyclonal targets Human PDX-1/IPF1 Affinity Purified Ab

View all literature mentions

Anti-CARBONIC ANHYDRASE II (RABBIT) Antibody - 200-401-136S (antibody)

RRID:AB_2612117

This unknown targets Carbonic Anhydrase II Antibody

View all literature mentions

Human Islet Research Network (HIRN) (data or information resource)

RRID:SCR_014393

Network helps to organize and support collaborative research related to loss of functional beta cell mass in Type 1 Diabetes (T1D). Project consists of four independent research initiatives: Consortium on Beta Cell Death and Survival (CBDS), Consortium on Human Islet Biomimetics (CHIB), Consortium on Modeling Autoimmune Interactions (CMAI), Consortium on Targeting and Regeneration (CTAR), and Human Pancreas Analysis Program (HPAP).

View all literature mentions

Anti-ghrelin (C-18) Antibody (antibody)

RRID:AB_2232479

This polyclonal targets GHRL

View all literature mentions

Human Islet Research Network (HIRN) (data or information resource)

RRID:SCR_014393

Network helps to organize and support collaborative research related to loss of functional beta cell mass in Type 1 Diabetes (T1D). Project consists of four independent research initiatives: Consortium on Beta Cell Death and Survival (CBDS), Consortium on Human Islet Biomimetics (CHIB), Consortium on Modeling Autoimmune Interactions (CMAI), Consortium on Targeting and Regeneration (CTAR), and Human Pancreas Analysis Program (HPAP).

View all literature mentions

Anti- Somatostatin (H-106) Antibody (antibody)

RRID:AB_2195930

This polyclonal targets Somatostatin

View all literature mentions

Anti-NKX6-1 polyclonal antibody (antibody)

RRID:AB_10673664

This polyclonal targets NKX6-1

View all literature mentions

NCAM1/CD56 antibody (antibody)

RRID:AB_2149421

This polyclonal targets NCAM1/CD56

View all literature mentions

Pancreatic Polypeptide antibody (antibody)

RRID:AB_1524152

This polyclonal targets Human Pancreatic Polypeptide

View all literature mentions

HLA DR antibody [TAL 1B5] (antibody)

RRID:AB_445401

This monoclonal targets HLA DR antibody [TAL 1B5]

View all literature mentions

Human PDX-1/IPF1 Affinity Purified Polyclonal Ab (antibody)

RRID:AB_355257

This polyclonal targets Human PDX-1/IPF1 Affinity Purified Ab

View all literature mentions

Anti-CARBONIC ANHYDRASE II (RABBIT) Antibody - 200-401-136S (antibody)

RRID:AB_2612117

This unknown targets Carbonic Anhydrase II Antibody

View all literature mentions