Co-expressing Pdx1 and Ngn3 induces few beta-like cells in the liver of mice.
We have assessed whether expressing pancreatic transcription factors Pdx1 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 beta-like cells which were marked by lacZ expression by X-gal staining. Insulin promoter assay showed that Pdx1 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 Pdx1 or Ngn3. Our results suggest that synergistic action of Pdx1 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.
Yoon
Soonsang
S
Division of Molecular Medicine, Children's Hospital, Department of Genetics, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: syoon@genetics.med.harvard.edu.
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D003001:Cloning, Molecular; D003920:Diabetes Mellitus / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein