Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry
Minghui Wu,
Michelle Y.Y. Lee,
Varun Bahl,
Daniel Traum,
Jonathan Schug,
Irina Kusmartseva,
Mark A. Atkinson,
Guanjie Fan,
Klaus H. Kaestner
Affiliations
Minghui Wu
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA; The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510720, China
Michelle Y.Y. Lee
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA; Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA
Varun Bahl
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
Daniel Traum
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
Jonathan Schug
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
Irina Kusmartseva
Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA
Mark A. Atkinson
Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA; Department of Pediatrics, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA; The Human Pancreas Analysis Program (RRID:SCR_016202)
Guanjie Fan
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510720, China; Department of Endocrinology, the Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510105, China
Klaus H. Kaestner
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
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.
