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

糖尿病是一组代谢紊乱，其特征是β细胞数量减少或β细胞功能障碍，导致血糖控制丧失。因此，再生β细胞的前景在糖尿病研究中具有巨大的兴趣。然而，由于对复杂的核转录因子网络的了解有限，体外多能干细胞衍生的β细胞通常缺乏功能。本研究的主要目的是从小鼠胰腺导管和ipsc衍生的胰腺祖细胞类器官中产生功能性胰岛素生成β细胞。我们的目标是通过RNA-seq在单细胞水平上表征分化途径，并确定在β细胞成熟的各个阶段活跃的主要信号通路。利用这些信息，我们将在iPSC向β细胞分化的过程中操纵这些途径，以获得具有更大功能和效率的β细胞。

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.