Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry

Summary: Type 2 diabetes mellitus (T2D) is a chronic age-related disorder characterized by hyperglycemia due to the failure of pancreatic beta cells to compensate for increased insulin demand. Despite decades of research, the pathogenic mechanisms underlying T2D remain poorly defined. Here, we use i...

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Autores principales: Minghui Wu, Michelle Y.Y. Lee, Varun Bahl, Daniel Traum, Jonathan Schug, Irina Kusmartseva, Mark A. Atkinson, Guanjie Fan, Klaus H. Kaestner
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Lenguaje:EN
Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/a8c0452dd1184df08e2878403748613b
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spelling oai:doaj.org-article:a8c0452dd1184df08e2878403748613b2021-11-04T04:29:09ZSingle-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry2211-124710.1016/j.celrep.2021.109919https://doaj.org/article/a8c0452dd1184df08e2878403748613b2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013929https://doaj.org/toc/2211-1247Summary: Type 2 diabetes mellitus (T2D) is a chronic age-related disorder characterized by hyperglycemia due to the failure of pancreatic beta cells to compensate for increased insulin demand. Despite decades of research, the pathogenic mechanisms underlying T2D remain poorly defined. Here, we use imaging mass cytometry (IMC) with a panel of 34 antibodies to simultaneously quantify markers of pancreatic exocrine, islet, and immune cells and stromal components. We analyze over 2 million cells from 16 pancreata obtained from donors with T2D and 13 pancreata from age-similar non-diabetic controls. In the T2D pancreata, we observe significant alterations in islet architecture, endocrine cell composition, and immune cell constituents. Thus, both HLA-DR-positive CD8 T cells and macrophages are enriched intra-islet in the T2D pancreas. These efforts demonstrate the utility of IMC for investigating complex events at the cellular level in order to provide insights into the pathophysiology of T2D.Minghui WuMichelle Y.Y. LeeVarun BahlDaniel TraumJonathan SchugIrina KusmartsevaMark A. AtkinsonGuanjie FanKlaus H. KaestnerElsevierarticleimaging mass cytometryimmunolabelinghistopathologytype 2 diabeteshuman pancreasmultiplexed imagingBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109919- (2021)
institution DOAJ
collection DOAJ
language EN
topic imaging mass cytometry
immunolabeling
histopathology
type 2 diabetes
human pancreas
multiplexed imaging
Biology (General)
QH301-705.5
spellingShingle imaging mass cytometry
immunolabeling
histopathology
type 2 diabetes
human pancreas
multiplexed imaging
Biology (General)
QH301-705.5
Minghui Wu
Michelle Y.Y. Lee
Varun Bahl
Daniel Traum
Jonathan Schug
Irina Kusmartseva
Mark A. Atkinson
Guanjie Fan
Klaus H. Kaestner
Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
description Summary: Type 2 diabetes mellitus (T2D) is a chronic age-related disorder characterized by hyperglycemia due to the failure of pancreatic beta cells to compensate for increased insulin demand. Despite decades of research, the pathogenic mechanisms underlying T2D remain poorly defined. Here, we use imaging mass cytometry (IMC) with a panel of 34 antibodies to simultaneously quantify markers of pancreatic exocrine, islet, and immune cells and stromal components. We analyze over 2 million cells from 16 pancreata obtained from donors with T2D and 13 pancreata from age-similar non-diabetic controls. In the T2D pancreata, we observe significant alterations in islet architecture, endocrine cell composition, and immune cell constituents. Thus, both HLA-DR-positive CD8 T cells and macrophages are enriched intra-islet in the T2D pancreas. These efforts demonstrate the utility of IMC for investigating complex events at the cellular level in order to provide insights into the pathophysiology of T2D.
format article
author Minghui Wu
Michelle Y.Y. Lee
Varun Bahl
Daniel Traum
Jonathan Schug
Irina Kusmartseva
Mark A. Atkinson
Guanjie Fan
Klaus H. Kaestner
author_facet Minghui Wu
Michelle Y.Y. Lee
Varun Bahl
Daniel Traum
Jonathan Schug
Irina Kusmartseva
Mark A. Atkinson
Guanjie Fan
Klaus H. Kaestner
author_sort Minghui Wu
title Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
title_short Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
title_full Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
title_fullStr Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
title_full_unstemmed Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
title_sort single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
publisher Elsevier
publishDate 2021
url https://doaj.org/article/a8c0452dd1184df08e2878403748613b
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