IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50611-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50611-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50611-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ryan J. Geusz & Allen Wang & Dieter K. Lam & Nicholas K. Vinckier & Konstantinos-Dionysios Alysandratos & David A. Roberts & Jinzhao Wang & Samy Kefalopoulou & Araceli Ramirez & Yunjiang Qiu & Joshua , 2021. "Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Vikash Chandra & Hazem Ibrahim & Clémentine Halliez & Rashmi B. Prasad & Federica Vecchio & Om Prakash Dwivedi & Jouni Kvist & Diego Balboa & Jonna Saarimäki-Vire & Hossam Montaser & Tom Barsby & Väin, 2022. "The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Qing Ma & Yini Xiao & Wenjun Xu & Menghan Wang & Sheng Li & Zhihao Yang & Minglu Xu & Tengjiao Zhang & Zhen-Ning Zhang & Rui Hu & Qiang Su & Fei Yuan & Tinghui Xiao & Xuan Wang & Qing He & Jiaxu Zhao , 2022. "ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Mostafa Bakhti & Aimée Bastidas-Ponce & Sophie Tritschler & Oliver Czarnecki & Marta Tarquis-Medina & Eva Nedvedova & Jessica Jaki & Stefanie J. Willmann & Katharina Scheibner & Perla Cota & Ciro Sali, 2022. "Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Xiaowen Lyu & M. Jordan Rowley & Michael J. Kulik & Stephen Dalton & Victor G. Corces, 2023. "Regulation of CTCF loop formation during pancreatic cell differentiation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Jennifer P. Nguyen & Timothy D. Arthur & Kyohei Fujita & Bianca M. Salgado & Margaret K. R. Donovan & Hiroko Matsui & Ji Hyun Kim & Agnieszka D’Antonio-Chronowska & Matteo D’Antonio & Kelly A. Frazer, 2023. "eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    7. Jolanta Chmielowiec & Wojciech J. Szlachcic & Diane Yang & Marissa A. Scavuzzo & Katrina Wamble & Alejandro Sarrion-Perdigones & Omaima M. Sabek & Koen J. T. Venken & Malgorzata Borowiak, 2022. "Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Yinglei Li & Ran Zheng & Lai Jiang & Chenchao Yan & Ran Liu & Luyi Chen & Wenwen Jin & Yuanyuan Luo & Xiafei Zhang & Jun Tang & Zhe Dai & Wei Jiang, 2024. "A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Shicheng Sun & Ali Motazedian & Jacky Y. Li & Kevin Wijanarko & Joe Jiang Zhu & Kothila Tharmarajah & Kathleen A. Strumila & Anton Shkaruta & L. Rayburn Nigos & Jacqueline V. Schiesser & Yi Yu & Paul , 2024. "Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Léon Gurp & Leon Fodoulian & Daniel Oropeza & Kenichiro Furuyama & Eva Bru-Tari & Anh Nguyet Vu & John S. Kaddis & Iván Rodríguez & Fabrizio Thorel & Pedro L. Herrera, 2022. "Generation of human islet cell type-specific identity genesets," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Frankie Poon & Rangarajan Sambathkumar & Roman Korytnikov & Yasaman Aghazadeh & Amanda Oakie & Paraish S. Misra & Farida Sarangi & M. Cristina Nostro, 2024. "Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50611-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.