In vitro direct reprogramming of mouse biliary epithelial cells towards an insulin-producing state

Abstract

Type I diabetes is an autoimmune disease resulting in the destruction of beta cells, the cell type in the body that produces insulin in the pancreas. Direct reprogramming can enable respecification of non-beta cells to produce insulin. The reprogramming vector, Ad-PNM, that expresses the genes Pdx1, Ngn3, and Mafa has reprogrammed non-beta cells of the pancreas and liver to produce insulin and restore normoglycemia in diabetic mice in vivo. Another possible approach is in vitro reprogramming with the same vector using cultured liver cells. Specifically, in this project biliary epithelial cells were isolated from mice, examined for Sox9 expression and treated with Ad-PNM to induce reprogramming.