dc.contributor.author | Vethe, Heidrun | en_US |
dc.contributor.author | Ghila, Luiza | en_US |
dc.contributor.author | Berle, Magnus | en_US |
dc.contributor.author | Hoareau, Laurence | en_US |
dc.contributor.author | Haaland, Øystein Ariansen | en_US |
dc.contributor.author | Scholz, Hanne | en_US |
dc.contributor.author | Paulo, Joao A. | en_US |
dc.contributor.author | Chera, Simona | en_US |
dc.contributor.author | Ræder, Helge | en_US |
dc.date.accessioned | 2020-05-20T17:04:16Z | |
dc.date.available | 2020-05-20T17:04:16Z | |
dc.date.issued | 2019-05-08 | |
dc.Published | Vethe H, Ghila L, Berle MF, Hoareau ML, Haaland ØA, Scholz HS, Paulo JA, Chera S, Ræder H. The effect of WnT pathway modulators on human iPSC-derived pancreatic beta cell maturation. Frontiers in Endocrinology. 2019;10:293 | eng |
dc.identifier.issn | 1664-2392 | |
dc.identifier.uri | https://hdl.handle.net/1956/22325 | |
dc.description.abstract | 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. | en_US |
dc.language.iso | eng | eng |
dc.publisher | Frontiers | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | eng |
dc.subject | human induced pluripotent stem cell | eng |
dc.subject | β-like cells | eng |
dc.subject | Wnt signaling pathway | eng |
dc.subject | tankyrase inhibition | eng |
dc.subject | in vitro maturation | eng |
dc.subject | Proteomics | eng |
dc.subject | TMT11-plex | eng |
dc.subject | adult human islets | eng |
dc.title | The effect of WnT pathway modulators on human iPSC-derived pancreatic beta cell maturation | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2019-12-13T13:43:57Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2019 The Author(s) | |
dc.identifier.doi | https://doi.org/10.3389/fendo.2019.00293 | |
dc.identifier.cristin | 1737683 | |
dc.source.journal | Frontiers in Endocrinology | |
dc.relation.project | Norges forskningsråd: 247577 | |