Deep Profiling of Tissue Ecosystems by Imaging Mass Cytometry

Tissues are complex ecosystems composed of multiple cell types and non-cellular components. Changes in cell type composition, cell functions and cell interactions within these ecosystems determine disease progression and response to therapy. Yet, technologies that enable comprehensive tissue profiling have emerged only recently. By coupling a high-resolution laser ablation system with a time-of-flight mass cytometer, Imaging Mass Cytometry (IMC) can detect over 40 proteins or protein modifications using metal-labeled antibodies as reporters. As compared to other analysis methods, IMC meets a unique niche by simultaneously collecting spatial information and providing information on cell functions and phenotypes.
We applied IMC to the study of pancreas sections from donors at different stages of Type 1 diabetes (T1D), a disorder resulting from the immune-mediated destruction of insulin-producing β cells located in pancreatic islets. This approach enabled simultaneous profiling of islet cells and of the immune cells that infiltrate these islets. We performed pseudotime analysis of islets through T1D progression in order to reconstruct the evolution of β cell loss and immune cell infiltration. Our analyses revealed that β cell destruction is preceded by alteration of the β cell phenotype. In addition, the recruitment of CD8+ and CD4+ T cells was simultaneous and depended on both disease stage and islet profile. The approaches described in our study demonstrate the value of highly multiplex imaging for improving our understanding of T1D pathogenesis and are applicable to a wide range of diseases, as will be illustrated by examples from breast cancer studies recently performed in our laboratory.

Nicolas Damond, Bodenmiller Lab, Department of Quantitative Biomedicine, University of Zurich, Switzerland

Nicolas Damond graduated from the University of Lausanne with an MSc in Genomics and Experimental Biology and received his PhD in Biology from the University of Geneva in 2015. Currently, he is working as a postdoctoral researcher in the lab of Prof. Bernd Bodenmiller at the University of Zurich. He has a long-standing research interest in the study of pancreatic islets in the context of type 1 diabetes. During his thesis work, he used transgenic mouse models and primary human islets to study islet cell type conversion after massive destruction of insulin-producing beta cells. He is now using Imaging Mass Cytometry to profile samples from donors with type 1 diabetes with the objective of reconstructing the parallel evolution of beta cells and islet-infiltrating immune cells through disease progression.