Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors

Nat Commun. 2024 Oct 9;15(1):8754. doi: 10.1038/s41467-024-53068-w.

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.

MeSH terms

  • Cell Differentiation* / drug effects
  • Enzyme Inhibitors / pharmacology
  • Glucose / metabolism
  • Humans
  • Insulin-Secreting Cells* / cytology
  • Insulin-Secreting Cells* / drug effects
  • Insulin-Secreting Cells* / metabolism
  • Pancreas / cytology
  • Pancreas / metabolism
  • Pluripotent Stem Cells* / cytology
  • Pluripotent Stem Cells* / drug effects
  • Pluripotent Stem Cells* / metabolism
  • Tankyrases* / antagonists & inhibitors
  • Tankyrases* / metabolism

Substances

  • Tankyrases
  • Glucose
  • Enzyme Inhibitors