Image_1_The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.TIFF (313.26 kB)

Image_1_The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.TIFF

Download (313.26 kB)
figure
posted on 08.05.2019, 09:35 by Heidrun Vethe, Luiza Ghila, Magnus Berle, Laurence Hoareau, Øystein A. Haaland, Hanne Scholz, Joao A. Paulo, Simona Chera, Helge Ræder

Current published protocols for targeted differentiation of human stem cells toward pancreatic β-cells fail to deliver sufficiently mature cells with functional properties comparable to human islet β-cells. We aimed to assess whether Wnt-modulation could promote the final protocol stages of β-cell maturation, building our hypothesis on our previous findings of Wnt activation in immature hiPSC-derived stage 7 (S7) cells compared to adult human islets and with recent data reporting a link between Wnt/PCP and in vitro β-cell maturation. In this study, we stimulated canonical and non-canonical Wnt signaling in hiPSC-derived S7 cells using syntetic proteins including WNT3A, WNT4, WNT5A and WNT5B, and we inhibited endogenous Wnt signaling with the Tankyrase inhibitor G007-LK (TKi). Whereas neither canonical nor non-canonical Wnt stimulation alone was able to mature hiPSC-derived S7 cells, WNT-inhibition with TKi increased the fraction of monohormonal cells and global proteomics of TKi-treated S7 cells showed a proteomic signature more similar to adult human islets, suggesting that inhibition of endogenous Wnt contributes toward final β-cell maturation.

History

References

Licence

Exports