Unknown

Dataset Information

0

STAT3 suppression and β-cell ablation enhance α-to-β reprogramming mediated by Pdx1.


ABSTRACT: As diabetes results from the absolute or relative deficiency of insulin secretion from pancreatic β cells, possible methods to efficiently generate surrogate β 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 α cells, by inducing defined transcription factors, such as PDX1 and MAFA, yet it is still challenging as to how surrogate β 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 α cells in vitro, and STAT3-null PDX1-expressing α cells in vivo resulted in efficient induction of α-to-β reprogramming, accompanied by the emergence of α-cell-derived insulin-producing cells with silenced glucagon expression. Whereas β-cell ablation by alloxan administration significantly increased the number of α-cell-derived insulin-producing cells by PDX1, STAT3 suppression resulted in no further increase in β-cell neogenesis after β-cell ablation. Thus, STAT3 modulation and β-cell ablation nonadditively enhance α-to-β reprogramming induced by PDX1, which may lead to the establishment of cell therapies for curing diabetes.

SUBMITTER: Wakabayashi Y 

PROVIDER: S-EPMC9741642 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

STAT3 suppression and β-cell ablation enhance α-to-β reprogramming mediated by Pdx1.

Wakabayashi Yuka Y   Miyatsuka Takeshi T   Miura Masaki M   Himuro Miwa M   Taguchi Tomomi T   Iida Hitoshi H   Nishida Yuya Y   Fujitani Yoshio Y   Watada Hirotaka H  

Scientific reports 20221210 1


As diabetes results from the absolute or relative deficiency of insulin secretion from pancreatic β cells, possible methods to efficiently generate surrogate β 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 α cells, by inducing defined transcription factors, such as PDX1 and MAFA, yet it is still challenging as to how surrogate β cells can be efficiently generated for est  ...[more]

Similar Datasets

| S-EPMC3286861 | biostudies-literature
| S-EPMC3950964 | biostudies-literature
| S-EPMC11304307 | biostudies-literature
| S-EPMC4960548 | biostudies-literature
| S-EPMC3582140 | biostudies-literature
| S-EPMC3417286 | biostudies-literature
| S-EPMC9984919 | biostudies-literature
| S-EPMC3780786 | biostudies-literature
| S-EPMC2776433 | biostudies-literature
2013-11-19 | GSE52258 | GEO