TET-dependent signaling of ß-cell underlies intrauterine hyperglycemia-induced glucose intolerance in offspring [scRNA-seq]
Epidemiologically, gestational diabetes mellitus (GDM) increases offspring's diabetes risk. Intrauterine hyperglycemia (IHG) is a typical characteristic of GDM, impairing offspring's glucose tolerance and insulin secretion, but the underlying mechanisms remain unclear. Here, we found IHG downregulates DNA demethylases Tet2/3 in fetal pancreatic islets. Pancreas-specific Tet2/3 double knockout (DKO) recapitulates the IHG effects. scRNA-seq analysis shows IHG or DKO downregulates ß-cell signature while upregulating d-cell signature. Overall design: To investigate the mechanisms of impairing offspring's glucose tolerance and insulin secretion in IHG offspring. Pancreatic islets from Tet2/3 double knockout mouse and IHG offspring was analyzed using scRNA-seq.