Identifying novel molecular mechanisms involved in the generation of new insulin-producing beta cells from adult stem / progenitor cells

Diabetes is a group of metabolic disorders characterised by a reduction in beta cell mass or beta cell dysfunction - resulting in a loss of glycaemic control. Consequently, the prospect of regenerating beta cells is of huge interest in diabetes research. However, beta cells derived in vitro from pluripotent stem cells commonly lack functionality due to a limited understanding of the complex nuclear transcription factor network. The primary aim of this investigation is to generate functional insulin-producing beta cells from murine pancreatic ductal and iPSC-derived pancreatic progenitor organoids. We aim to characterise the differentiation pathway at the single-cell level by RNA-seq and identify the major signalling pathways active during various stages of beta cell maturation. Using this information, we will manipulate these pathways during an established iPSC to beta cell differentiation protocol in order to derive beta cells with greater functionality and efficiency.