| First Author | Wakabayashi Y | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 21419 |
| PubMed ID | 36496541 | Mgi Jnum | J:337677 |
| Mgi Id | MGI:7410563 | Doi | 10.1038/s41598-022-25941-5 |
| Citation | Wakabayashi Y, et al. (2022) STAT3 suppression and beta-cell ablation enhance alpha-to-beta reprogramming mediated by Pdx1. Sci Rep 12(1):21419 |
| abstractText | As diabetes results from the absolute or relative deficiency of insulin secretion from pancreatic beta cells, possible methods to efficiently generate surrogate beta cells have attracted a lot of efforts. To date, insulin-producing cells have been generated from various differentiated cell types in the pancreas, such as acinar cells and alpha cells, by inducing defined transcription factors, such as PDX1 and MAFA, yet it is still challenging as to how surrogate beta cells can be efficiently generated for establishing future regenerative therapies for diabetes. In this study, we demonstrated that the exogenous expression of PDX1 activated STAT3 in alpha cells in vitro, and STAT3-null PDX1-expressing alpha cells in vivo resulted in efficient induction of alpha-to-beta reprogramming, accompanied by the emergence of alpha-cell-derived insulin-producing cells with silenced glucagon expression. Whereas beta-cell ablation by alloxan administration significantly increased the number of alpha-cell-derived insulin-producing cells by PDX1, STAT3 suppression resulted in no further increase in beta-cell neogenesis after beta-cell ablation. Thus, STAT3 modulation and beta-cell ablation nonadditively enhance alpha-to-beta reprogramming induced by PDX1, which may lead to the establishment of cell therapies for curing diabetes. |
