We have assessed whether expressing pancreatic transcription factors PdxI and Ngn3 in the liver could induce beta-like cells for curing type I diabetes. When co-expressed in the liver of insulin reporter mice using adenovirus, few cells in the liver were turned into betalike cells which were marked by lacZ expression by X-gal staining. Insulin promoter assay showed that Pdxl highly activates insulin promoter when combined with Ngn3. In ex vivo experiments to determine permissiveness of stem/progenitor and fully differentiated cells by ectopic transcription factors, it was found that more islet genes were induced in ES or bone marrow SP cells than fully differentiated NIH3T3 or MEF cells by PdxI or Ngn3. Our results suggest that synergistic action of PdxI and Ngn3 on inducing various islet genes as well as cell intrinsic factors played a crucial role in directing few liver cells into beta-like cells in vivo. (c) 2007 Elsevier Inc. All rights reserved.