Type 1 diabetes (T1D) happens when the immune system attacks and destroys the insulin-producing beta-cells in the pancreas, which are contained in the islets of Largenhans. Research has shown that beta-cells within islets are not all identical: some differ from others in the genes they use and in how well they work. We think that these differences, referred to as “heterogeneity”, affect how fast these cells are lost in T1D by making some beta-cells more susceptible to destruction by the immune system. Scientists are growing islets in the lab from stem cells (SC-Islets), hoping that these could be transplanted to cure T1D. We want to find out whether these differences between beta-cells are fully represented in SC-islets, as this may affect how well SC-islets work. For this, we need to better understand the heterogeneity of beta-cells in the islets of people with and without T1D, and whether it is similar to healthy SC-islets, and how does it change in inflammatory conditions.
We are interested in a group of very small molecules called microRNAs. MicroRNAs help control which proteins a cell makes and are important for beta-cell development and function. However, no one has yet looked properly at whether microRNAs vary between different beta-cells within islets of Langerhans in the human pancreas during T1D.
The project has two main questions:
–Do miRNAs behave differently in different subtypes of beta-cells in people living with T1D compared to those without it, and during disease progression?
–Are miRNAs different between subtypes of beta-cells in SC-islets compared with human islets?
As part of aim 1, we will use pancreas samples from organ donors without diabetes, donors at risk of T1D, and donors with T1D. Using advanced imaging methods, we will analyze selected miRNAs directly in pancreas sections and examine which cells contain them, where they are located, and how they change during disease. We will also study how these patterns relate to insulin expression and the presence of immune cells. As part of aim 2, these images will be compared with similar stainings of SC-islets.
Understanding these differences will help us understand why some beta-cells may be more vulnerable than others in T1D. Thus, this work will help us identify opportunities to prevent or decelerate beta-cell destruction in T1D or improve lab-made beta-cells for transplantation.
