{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:34:51Z","timestamp":1778816091637,"version":"3.51.4"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5903","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,11,7]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1126\/science.1162494","type":"journal-article","created":{"date-parts":[[2008,9,25]],"date-time":"2008-09-25T20:45:27Z","timestamp":1222375527000},"page":"945-949","source":"Crossref","is-referenced-by-count":1291,"title":["Induced Pluripotent Stem Cells Generated Without Viral Integration"],"prefix":"10.1126","volume":"322","author":[{"given":"Matthias","family":"Stadtfeld","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."},{"name":"Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02115, USA."},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Nagaya","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."},{"name":"Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02115, USA."},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Utikal","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."},{"name":"Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02115, USA."},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon","family":"Weir","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."},{"name":"Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02115, USA."},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Hochedlinger","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."},{"name":"Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02115, USA."},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"e_1_3_1_3_2","unstructured":"M. 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Hock for critical comments on the manuscript and L. Prickett and K. Folz-Donahue for expert help with flow cytometry. We are especially grateful to J. Lee of the Harvard Gene Therapy Initiative for help with the generation of adenoviral vectors. M.S. was supported by a Schering postdoctoral fellowship J.U. was supported by a Mildred Scheel postdoctoral fellowship and M.N. and G.W. received support from the Juvenile Diabetes Research Foundation. Support to K.H. was from the NIH Director's Innovator Award the Harvard Stem Cell Institute the Kimmel Foundation and the V Foundation. The authors are filing a patent based on the results reported in this paper."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1162494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:47:35Z","timestamp":1704862055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1162494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11,7]]},"references-count":30,"journal-issue":{"issue":"5903","published-print":{"date-parts":[[2008,11,7]]}},"alternative-id":["10.1126\/science.1162494"],"URL":"https:\/\/doi.org\/10.1126\/science.1162494","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1124065.581185","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11,7]]}}}