Vethe, Heidrun Ghila, Luiza Berle, Magnus Hoareau, Laurence Haaland, Øystein A. Scholz, Hanne Paulo, Joao A. Chera, Simona Ræder, Helge Image_1_The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.TIFF <p>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.</p> human induced pluripotent stem cell;β-like cells;Wnt signaling pathway;tankyrase inhibition;in vitro maturation;proteomics;TMT11-plex;adult human islets 2019-05-08
    https://frontiersin.figshare.com/articles/figure/Image_1_The_Effect_of_Wnt_Pathway_Modulators_on_Human_iPSC-Derived_Pancreatic_Beta_Cell_Maturation_TIFF/8094203
10.3389/fendo.2019.00293.s001