Type 1 diabetes mellitus (T1D) is a complex autoimmune condition which is globally raising, it is influenced by genetic predisposition and environmental factors such as dietary changes and potential exposure to viruses or toxins. Single–cell methods have recently shown that endocrine islet cells are molecularly and functionally heterogeneous, and that cell–to–cell interactions within islets are critical in normal physiological function and in the development of disease like T1D. However, to date there are only a few approaches available to obtain accurate molecular and functional characterization of islet cells in their tissue context. In this project, we will combine spatial transcriptomics with functional imaging in pancreatic tissue slices and use this approach to gain novel insights into the physiological and genomic changes that take place in pancreatic islets during onset of T1D. We hypothesize that some of these changes are structured and dependent on the cellular microenvironment. This novel methodology will permit the characterization of β–and α–cell subpopulations in their tissue context during progression to T1D and link changes in cell functionality to their molecular profile. The identification of transcriptomic regulators of coordinated islet cell function and mechanisms of disruption during T1D onset will be used at a later stage to identify new diagnostic biomarkers of islet disruption and β–cell damage and potential therapeutic interventions.
