2. Academic Validation
  3. Directed differentiation of pancreatic δ cells from human pluripotent stem cells

Directed differentiation of pancreatic δ cells from human pluripotent stem cells

  • Nat Commun. 2024 Jul 27;15(1):6344. doi: 10.1038/s41467-024-50611-7.
Lihua Chen # 1 2,  Nannan Wang # 2 3,  Tongran Zhang # 2 4,  Feng Zhang 2,  Wei Zhang 2,  Hao Meng 1 2,  Jingyi Chen 2 5,  Zhiying Liao 1 2,  Xiaopeng Xu 2,  Zhuo Ma 6,  Tao Xu 7 8,  Huisheng Liu 9 10 11 12
Affiliations

Affiliations

  • 1 School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 2 Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • 3 College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 4 Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 5 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, China.
  • 6 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 7 School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China. xutao@ibp.ac.cn.
  • 8 Guangzhou National Laboratory, Guangzhou, Guangdong, China. xutao@ibp.ac.cn.
  • 9 School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China. Liu_huisheng@gzlab.ac.cn.
  • 10 Guangzhou National Laboratory, Guangzhou, Guangdong, China. Liu_huisheng@gzlab.ac.cn.
  • 11 College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China. Liu_huisheng@gzlab.ac.cn.
  • 12 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, China. Liu_huisheng@gzlab.ac.cn.
  • # Contributed equally.
PMID: 39068220 DOI: 10.1038/s41467-024-50611-7
Abstract

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.

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