Induced Pluripotent Stem Cells Generated Without Viral Integration | Zendy

Matthias Stadtfeld | Zendy; Masaki Nagaya | Zendy; Jochen Utikal | Zendy; Gordon C. Weir | Zendy; Konrad Hochedlinger | Zendy

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Induced Pluripotent Stem Cells Generated Without Viral Integration

Author(s) -

Matthias Stadtfeld,

Masaki Nagaya,

Jochen Utikal,

Gordon C. Weir,

Konrad Hochedlinger

Publication year - 2008

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1162494

Subject(s) - induced pluripotent stem cell , reprogramming , sox2 , klf4 , biology , embryonic stem cell , stem cell , microbiology and biotechnology , somatic cell , induced stem cells , embryoid body , homeobox protein nanog , insertional mutagenesis , genetics , gene , genome

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.

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