Dataset Information
Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors.
Ontology highlight
ABSTRACT: Background
STAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, whereas an activating STAT3 mutation has been linked to impaired ?-cell function.Methods
The role of STAT3 in ?-cell neogenesis, induced by the exogenous expression of Pdx1, Neurog3, and Mafa, was analyzed in vitro and in vivo.Findings
The expression of phosphorylated STAT3 (pSTAT3) was induced in both Pdx1-expressing and Mafa-expressing cells, but most of the induced ? cells were negative for pSTAT3. The suppression of STAT3 signaling, together with exogenously expressed Pdx1, Neurog3, and Mafa, significantly increased the number of reprogrammed ? cells in vitro and in vivo, enhanced the formation of islet-like clusters in mice, and ameliorated hyperglycemia in diabetic mice.Interpretation
These findings suggest that STAT3 inhibition promotes cellular reprogramming into ?-like cells, orchestrated by defined transcription factors, which may lead to the establishment of cell therapies for curing diabetes. FUND: JSPS, MEXT, Takeda Science Foundation, Suzuken Memorial Foundation, Astellas Foundation for Research on Metabolic Disorders, Novo Nordisk, Eli Lilly, MSD, Life Scan, Novartis, and Takeda.
SUBMITTER: Miura M
PROVIDER: S-EPMC6197741 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors.
EBioMedicine 20180925
<h4>Background</h4>STAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, whereas an activating STAT3 mutation has been linked to impaired β-cell function.<h4>Methods</h4>The role of STAT3 in β-cell neogenesis, induced by the exogenous expression of Pdx1, Neurog3, and Mafa, was analyzed in vitro and in vivo.<h4>Findings</h4>The expression of phosphorylated STAT3 (pSTAT3) was induced in both Pdx1-expressing and Mafa-expressing cells, but most of the induced ...[more]