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Induced pluripotent stem cells generated without viral integration.

Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells.

Pubmed ID: 18818365

Authors

  • Stadtfeld M
  • Nagaya M
  • Utikal J
  • Weir G
  • Hochedlinger K

Journal

Science (New York, N.Y.)

Publication Data

November 7, 2008

Associated Grants

  • Agency: NIH HHS, Id: DP2 OD003266

Mesh Terms

  • Adenoviridae
  • Animals
  • Cell Differentiation
  • Cell Line
  • Cellular Reprogramming
  • Chimera
  • Cloning, Molecular
  • Female
  • Fibroblasts
  • Genes, myc
  • Genetic Vectors
  • Hepatocytes
  • Kruppel-Like Transcription Factors
  • Liver
  • Male
  • Mice
  • Mice, SCID
  • Octamer Transcription Factor-3
  • Pluripotent Stem Cells
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Teratoma
  • Transgenes
  • Virus Integration