Identification of differential isoform usage in type 1 diabetic mouse islets

Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by the loss of pancreatic beta cells due to immune destruction. Despite its prevalence, the exact cause remains unknown, posing challenges for effective treatments. Our project seeks to understand the root cause of T1D by focusing on the insulin-producing beta cells. Loss of these beta cells leads to the disrupted blood sugar levels in T1D. Recent studies have indicated that changes in the way RNA is processed could contribute to beta cell dysfunction in T1D. Our project aims to characterize changes in RNA processing using single cell long-read RNA sequencing. Traditional techniques for characterizing RNA changes have two major limitations. First, they pool all pancreatic cells together and lose beta cell specific information. Second, they rely on technologies that can't assay full-length RNA. Our proposed method will sequence full-length RNA molecules in individual cells which will provide information about how they are regulated at a single cell level, helping us understand the intricate details of T1D development. Our preliminary experiments conducted in mice have shown promising results. We have successfully used the proposed method to identify genetic differences between beta cells and other cells in the pancreas. Now we want to use this proof of principle to explore what genetic changes occur in beta cells during an immune response in mice. Once we identify these genetic changes, we plan to characterize their impact on beta cell development and function. Overall, this research addresses a critical gap in understanding T1D development.