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

鉴定涉及从成体干细胞/祖细胞生成新的胰岛素产生β细胞的新分子机制

• 批准号: 1930833
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1930833
• 关键词: Identifying; novel; molecular; mechanisms; involved

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.

糖尿病是一组代谢紊乱，其特征在于β细胞量减少或β细胞功能障碍-导致血液控制丧失。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理解有限，体外衍生自多能干细胞的β细胞通常缺乏功能性。本研究的主要目的是从鼠胰腺导管和iPSC衍生的胰腺祖细胞类器官产生功能性胰岛素产生β细胞。我们的目标是通过RNA-seq在单细胞水平上研究分化途径，并确定在β细胞成熟的各个阶段活跃的主要信号传导途径。利用这些信息，我们将在已建立的iPSC向β细胞分化方案中操纵这些途径，以获得具有更大功能和效率的β细胞。