Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors

Frankie Poon, Rangarajan Sambathkumar, Roman Korytnikov, Yasaman Aghazadeh, Amanda Oakie, Paraish S. Misra, Farida Sarangi and M. Cristina Nostro ()
Additional contact information
Frankie Poon: University Health Network
Rangarajan Sambathkumar: University Health Network
Roman Korytnikov: University Health Network
Yasaman Aghazadeh: University Health Network
Amanda Oakie: University Health Network
Paraish S. Misra: University Health Network
Farida Sarangi: University Health Network
M. Cristina Nostro: University Health Network

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53068-w

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