title: Hybrid cell extinction and re-expression of Oct-3 function correlates with differentiation potential.
abstract: The Oct-3 gene is expressed in highly undifferentiated cells and is implicated in mammalian early embryogenesis. We have generated a series of hybrid cells between pluripotent embryonal carcinoma cells (Oct-3+) and fibroblasts (Oct-3-), and have studied the regulation and function of Oct-3. Upon fusion, the hybrid cells differentiated to nestin+/Brn-2+ cells resembling neuroepithelial stem cells. Expression of Oct-3 was extinguished at the transcriptional level in all the hybrid cells examined. The Oct-3 modulating activity required for the Oct-3-mediated enhancer activation was also extinguished. When the Oct-3 transactivating function was introduced into the hybrid cells, they transformed into morphologically distinct nestin-/Brn-2- cells ('revertants'). When the 'revertant' cells subsequently lost Oct-3 expression, they differentiated back to nestin+/Brn-2+ cells. The close correlation between the phenotypic changes and the gain/loss of Oct-3 function indicates that Oct-3 can induce dedifferentiation of the neural cells.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shimazaki
authors.forename: H
authors.initials: H
authors.lastname: Okazawa
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Tamai
authors.forename: R D
authors.initials: RD
authors.lastname: McKay
authors.forename: M
authors.initials: M
authors.lastname: Muramatsu
authors.forename: H
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D054278:Embryonal Carcinoma Stem Cells; D006822:Hybrid Cells / Q000166:cytology*; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000166:cytology; D050814:Octamer Transcription Factor-3; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors; D004247:DNA