The Role of Alternative Splicing in the Differentiation of Pancreatic β cells

Pancreatic β cells are crucial to glucose regulation because they produce and secrete insulin, which enables cells to take up glucose from the blood. Dysregulation of this process would lead to diabetes, a major health challenge in Qatar. Therefore, proper differentiation of pancreatic cells into mature insulin-producing β cells is critical to healthy glucose regulation. One of the mechanisms that govern differentiation is alternative splicing (AS), yet specific AS alterations in pancreatic cells have not been previously identified, and their relevance to b cell function remains unknown. These changes may be contributing to b cells function, and therefore, studying them can provide a better understanding of the pathogenesis of diabetes. We have identified significant AS alterations between pancreatic cells at different stages of cell differentiation – pancreatic progenitors and mature pancreatic islets. EXOC7 and TMEM63B are two genes that showed alternative splicing changes between pancreatic progenitors and mature islets, and that have been implicated in important functions in the cell. We found that alternative splicing in TMEM63B changes in pancreatic cells that do not differentiate properly, which suggests that TMEM63B splicing may be a marker of pancreatic cell differentiation.