Directed differentiation of pancreatic δ cells from human pluripotent stem cells.

Autor: Chen, Lihua, Wang, Nannan, Zhang, Tongran, Zhang, Feng, Zhang, Wei, Meng, Hao, Chen, Jingyi, Liao, Zhiying, Xu, Xiaopeng, Ma, Zhuo, Xu, Tao, Liu, Huisheng
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Zdroj: Nature Communications; 7/27/2024, Vol. 15 Issue 1, p1-22, 22p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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