Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors
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.
Authors
- Farida Sarangi (ORCID: https://orcid.org/0000-0003-4935-1234)
- Frankie Poon
- Paraish S. Misra (ORCID: https://orcid.org/0000-0002-0514-8560)
- Roman Korytnikov
- M. Cristina Nostro (ORCID: https://orcid.org/0000-0003-1166-8252)
- Amanda Oakie (ORCID: https://orcid.org/0000-0002-4749-4269)
- Rangarajan Sambathkumar (ORCID: https://orcid.org/0000-0002-2751-3143)
- Yasaman Aghazadeh (ORCID: https://orcid.org/0000-0003-0642-0631)
Institutions
- University Health Network (CA)
- University of Toronto (CA)
- Sana Biotechnology (United States) (US)
- Montreal Clinical Research Institute (CA)
- McMaster University (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-09
- DOI
- https://doi.org/10.1038/s41467-024-53068-w
- Citations
- 4
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 2.29
Funders
- Eli Lilly and Company
- Leona M. and Harry B. Helmsley Charitable Trust
- Juvenile Diabetes Research Foundation United States of America
- Juvenile Diabetes Research Foundation Canada
- Toronto General and Western Hospital Foundation
- Canadian Society of Transplantation
- Eli Lilly Canada
- Toronto General Hospital Research Institute, University Health Network
- Natural Sciences and Engineering Research Council of Canada
- Banting and Best Diabetes Centre, University of Toronto
- CIHR Skin Research Training Centre