Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors.

Autor: Poon F; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada.; Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Sana Biotechnology, 300 Technology Square, Cambridge, MA, 02139, USA., Sambathkumar R; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada.; Allarta Life Science Inc., 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada., Korytnikov R; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada.; Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada., Aghazadeh Y; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada.; Montreal Clinical Research Institute (IRCM), University of Montreal, Department of Medicine, Montreal, H2W 1R7, QC, Canada., Oakie A; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada., Misra PS; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada.; Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Department of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada., Sarangi F; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada., Nostro MC; McEwen Stem Cell Institute, University Health Network, Toronto, ON, M5G 1L7, Canada. cristina.nostro@uhn.ca.; Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. cristina.nostro@uhn.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 09; Vol. 15 (1), pp. 8754. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1038/s41467-024-53068-w
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: