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Directed differentiation of pancreatic δ cells from human pluripotent stem cells

Author

Listed:
  • Lihua Chen

    (Guangzhou Medical University
    Guangzhou National Laboratory)

  • Nannan Wang

    (Guangzhou National Laboratory
    Huazhong University of Science and Technology)

  • Tongran Zhang

    (Guangzhou National Laboratory
    Huazhong University of Science and Technology)

  • Feng Zhang

    (Guangzhou National Laboratory)

  • Wei Zhang

    (Guangzhou National Laboratory)

  • Hao Meng

    (Guangzhou Medical University
    Guangzhou National Laboratory)

  • Jingyi Chen

    (Guangzhou National Laboratory
    South China University of Technology, Guangzhou International Campus)

  • Zhiying Liao

    (Guangzhou Medical University
    Guangzhou National Laboratory)

  • Xiaopeng Xu

    (Guangzhou National Laboratory)

  • Zhuo Ma

    (Institute of Biophysics, Chinese Academy of Sciences)

  • Tao Xu

    (Guangzhou Medical University
    Guangzhou National Laboratory)

  • Huisheng Liu

    (Guangzhou Medical University
    Guangzhou National Laboratory
    Huazhong University of Science and Technology
    South China University of Technology, Guangzhou International Campus)

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.

Suggested Citation

  • Lihua Chen & Nannan Wang & Tongran Zhang & Feng Zhang & Wei Zhang & Hao Meng & Jingyi Chen & Zhiying Liao & Xiaopeng Xu & Zhuo Ma & Tao Xu & Huisheng Liu, 2024. "Directed differentiation of pancreatic δ cells from human pluripotent stem cells," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50611-7
    DOI: 10.1038/s41467-024-50611-7
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    References listed on IDEAS

    as
    1. Elisa Vergari & Jakob G. Knudsen & Reshma Ramracheya & Albert Salehi & Quan Zhang & Julie Adam & Ingrid Wernstedt Asterholm & Anna Benrick & Linford J. B. Briant & Margarita V. Chibalina & Fiona M. Gr, 2019. "Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Muhmmad Omar-Hmeadi & Per-Eric Lund & Nikhil R. Gandasi & Anders Tengholm & Sebastian Barg, 2020. "Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Pascal Boer & Nicole M. Pirozzi & Anouk H. G. Wolters & Jeroen Kuipers & Irina Kusmartseva & Mark A. Atkinson & Martha Campbell-Thompson & Ben N. G. Giepmans, 2020. "Large-scale electron microscopy database for human type 1 diabetes," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    4. Rafael Arrojo e Drigo & Stefan Jacob & Concha F. García-Prieto & Xiaofeng Zheng & Masahiro Fukuda & Hoa Tran Thi Nhu & Olga Stelmashenko & Flavia Letícia Martins Peçanha & Rayner Rodriguez-Diaz & Eric, 2019. "Author Correction: Structural basis for delta cell paracrine regulation in pancreatic islets," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
    5. Quinn P. Peterson & Adrian Veres & Lihua Chen & Michael Q. Slama & Jennifer H. R. Kenty & Shaimaa Hassoun & Matthew R. Brown & Haiqiang Dou & Caden D. Duffy & Quan Zhou & Aleksey V. Matveyenko & Björn, 2020. "A method for the generation of human stem cell-derived alpha cells," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    6. Adrian Veres & Aubrey L. Faust & Henry L. Bushnell & Elise N. Engquist & Jennifer Hyoje-Ryu Kenty & George Harb & Yeh-Chuin Poh & Elad Sintov & Mads Gürtler & Felicia W. Pagliuca & Quinn P. Peterson &, 2019. "Charting cellular identity during human in vitro β-cell differentiation," Nature, Nature, vol. 569(7756), pages 368-373, May.
    7. Romana Bohuslavova & Valeria Fabriciova & Ondrej Smolik & Laura Lebrón-Mora & Pavel Abaffy & Sarka Benesova & Daniel Zucha & Lukas Valihrach & Zuzana Berkova & Frantisek Saudek & Gabriela Pavlinkova, 2023. "NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Rafael Arrojo e Drigo & Stefan Jacob & Concha F. García-Prieto & Xiaofeng Zheng & Masahiro Fukuda & Hoa Tran Thi Nhu & Olga Stelmashenko & Flavia Letícia Martins Peçanha & Rayner Rodriguez-Diaz & Eric, 2019. "Structural basis for delta cell paracrine regulation in pancreatic islets," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    9. Zhuo Ma & Xiaofei Zhang & Wen Zhong & Hongyan Yi & Xiaowei Chen & Yinsuo Zhao & Yanlin Ma & Eli Song & Tao Xu, 2023. "Deciphering early human pancreas development at the single-cell level," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
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