Subcellular mapping of cell types in healthy human pancreatic islets

Abstract: Pancreatic islets are composed of endocrine cells that secrete hormones essential for blood-glucose homeostasis. Prior research has revealed that the gene expression and functionality of human islet cells is heterogenous. However, it is not currently understood how the heterogeneity correlates to normal islet cell function and dysfunction in diabetes pathogenesis. Subsequently, an international collaborative project has been initiated to elucidate what constitutes islet cell heterogeneity from a transcriptional, proteomic, and functional perspective in both health and disease. In this study, a highly multiplex tissue image assay was developed to allow for the study of the localization and distribution of proteins previously identified to correlate with functional activity and heterogeneity in islet cells using the CO-Detection by indEXing (CODEX) platform. In total, 22 proteins were studied simultaneously of which 10 were specifically expressed in islet cells. These included generic pancreatic markers such as C-peptide (C-pep) marking insulin-secreting β-cells, glucagon (GCG) and somatostatin (SST), but also less well-characterized proteins such as Shisa like 2B (FAM159B) and Neural proliferation, differentiation and control 1 (NPDC1). The multiplex tissue imaging allowed for single-cell analysis of protein expression in human islet cells showing that most islet specific proteins were heterogeneously expressed. The observations made in this study serves as a validation to that the human islet microenvironment is highly complex due to islet cell heterogeneity. Additionally, the study demonstrated that multiplex tissue imaging has the potential to reveal novel cell types and interactions.