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A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry


Damond, Nicolas; Engler, Stefanie; Zanotelli, Vito R T; Schapiro, Denis; Wasserfall, Clive H; Kusmartseva, Irina; Nick, Harry S; Thorel, Fabrizio; Herrera, Pedro L; Atkinson, Mark A; Bodenmiller, Bernd (2019). A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry. Cell Metabolism, 29(3):755-768.e5.

Abstract

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β cells. A comprehensive picture of the changes during T1D development is lacking due to limited sample availability, inability to sample longitudinally, and the paucity of technologies enabling comprehensive tissue profiling. Here, we analyzed 1,581 islets from 12 human donors, including eight with T1D, using imaging mass cytometry (IMC). IMC enabled simultaneous measurement of 35 biomarkers with single-cell and spatial resolution. We performed pseudotime analysis of islets through T1D progression from snapshot data to reconstruct the evolution of β cell loss and insulitis. Our analyses revealed that β cell destruction is preceded by a β cell marker loss and by recruitment of cytotoxic and helper T cells. The approaches described herein demonstrate the value of IMC for improving our understanding of T1D pathogenesis, and our data lay the foundation for hypothesis generation and follow-on experiments.

Abstract

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β cells. A comprehensive picture of the changes during T1D development is lacking due to limited sample availability, inability to sample longitudinally, and the paucity of technologies enabling comprehensive tissue profiling. Here, we analyzed 1,581 islets from 12 human donors, including eight with T1D, using imaging mass cytometry (IMC). IMC enabled simultaneous measurement of 35 biomarkers with single-cell and spatial resolution. We performed pseudotime analysis of islets through T1D progression from snapshot data to reconstruct the evolution of β cell loss and insulitis. Our analyses revealed that β cell destruction is preceded by a β cell marker loss and by recruitment of cytotoxic and helper T cells. The approaches described herein demonstrate the value of IMC for improving our understanding of T1D pathogenesis, and our data lay the foundation for hypothesis generation and follow-on experiments.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Quantitative Biomedicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Physiology
Life Sciences > Molecular Biology
Life Sciences > Cell Biology
Uncontrolled Keywords:Cell Biology, Physiology, Molecular Biology
Language:English
Date:31 January 2019
Deposited On:07 Feb 2020 10:39
Last Modified:29 Jul 2020 13:40
Publisher:Cell Press (Elsevier)
ISSN:1550-4131
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.cmet.2018.11.014
PubMed ID:30713109

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