Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene expression in ES-derived differentiated cells.
Embryonic stem (ES) cells can differentiate into many cell types. Recent reports have shown that ES cells can differentiate into insulin-producing cells. We have established an ES cell line in which exogenous Pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to produce insulin-producing cells. The Pdx-1 expressing final differentiated insulin-positive cells can be maintained for more than 2 months. However, in spite of their induced expression of Pdx-1, the repeated passages of cells lost their capacity to express insulin and NeuroD1 gene. Forced expression of NeuroD1 gene by adenoviral vector in these cells restored the expression of insulin. These results suggested that maintenance of the property of insulin-producing cells derived from ES cells could be achieved by synergistic expression of Pdx-1 and NeuroD1.
Saitoh
Koichi
K
Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Yamato
Eiji
E
Miyazaki
Satsuki
S
Miyazaki
Jun-Ichi
J
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics*; D051379:Mice; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D012313:RNA; D015534:Trans-Activators; C093970:NEUROD1 protein, human; C501008:Neurod1 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein