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Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors

Author

Listed:
  • Frankie Poon

    (University Health Network
    University of Toronto
    300 Technology Square)

  • Rangarajan Sambathkumar

    (University Health Network
    Allarta Life Science Inc.)

  • Roman Korytnikov

    (University Health Network
    University of Toronto)

  • Yasaman Aghazadeh

    (University Health Network
    Department of Medicine)

  • Amanda Oakie

    (University Health Network)

  • Paraish S. Misra

    (University Health Network
    University of Toronto
    University of Toronto)

  • Farida Sarangi

    (University Health Network)

  • M. Cristina Nostro

    (University Health Network
    University of Toronto)

Abstract

Human pluripotent stem cells (hPSCs) have the potential to differentiate into various cell types, including pancreatic insulin-producing β cells, which are crucial for developing therapies for diabetes. However, current methods for directing hPSC differentiation towards pancreatic β-like cells are often inefficient and produce cells that do not fully resemble the native counterparts. Here, we report that highly selective tankyrase inhibitors, such as WIKI4, significantly enhances pancreatic differentiation from hPSCs. Our results show that WIKI4 promotes the formation of pancreatic progenitors that give rise to islet-like cells with improved β-like cell frequencies and glucose responsiveness compared to our standard cultures. These findings not only advance our understanding of pancreatic development, but also provide a promising new tool for generating pancreatic cells for research and potential therapeutic applications.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53068-w
    DOI: 10.1038/s41467-024-53068-w
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    References listed on IDEAS

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