Directed differentiation of pancreatic δ cells from human pluripotent stem cells

作者：Lihua Chen, Nannan Wang, Tongran Zhang, Feng Zhang, Wei Kevin Zhang, Hao Meng, Jingyi Chen, Zhiying Liao, Xiaopeng Xu, Zhuo Ma, Tao Xu, Huisheng Liu · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-50611-7 · 被引用次数：15 · 研究领域：Pancreatic function and diabetes、Diabetes Management and Research、Diabetes and associated disorders

Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured β cells and mouse β cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes. Human pancreatic δ cells play important roles in the balance of pancreatic hormones. Here, the authors develop a directed differentiation method to generate in vitro and in vivo functional δ cells from human stem cells by combining FGF2 with FGF7.