Direct reprogramming of non-human primate bile ducts in vivo and human pancreatic ductal cells in vitro towards a B-cell state

Abstract

Direct reprogramming of one cell type into another without passing through a pluripotent state can be promoted by expressing transcription factors necessary during embryonic development for the specification of the new cell-type. The transcription factors Pdx1, Ngn3, and MafA when expressed together by an adenoviral vector (Ad-PNM) are able to directly reprogram Sox9+ cells lining the bile ducts of mice into insulin expressing cells that restore glucose homeostasis in diabetic mice. As an extension of this work, in this research project Ad-PNM was administered in vivo to the liver of a non-human primate and also to human pancreatic ductal cells in vitro.