%0 Figure %A Vethe, Heidrun %A Ghila, Luiza %A Berle, Magnus %A Hoareau, Laurence %A Haaland, Øystein A. %A Scholz, Hanne %A Paulo, Joao A. %A Chera, Simona %A Ræder, Helge %D 2019 %T Image_1_The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.TIFF %U https://frontiersin.figshare.com/articles/figure/Image_1_The_Effect_of_Wnt_Pathway_Modulators_on_Human_iPSC-Derived_Pancreatic_Beta_Cell_Maturation_TIFF/8094203 %R 10.3389/fendo.2019.00293.s001 %2 https://frontiersin.figshare.com/ndownloader/files/15102956 %K human induced pluripotent stem cell %K β-like cells %K Wnt signaling pathway %K tankyrase inhibition %K in vitro maturation %K proteomics %K TMT11-plex %K adult human islets %X

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.

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