Research abstract
Article abstract
Nature Biotechnology 26, 1269 - 1275 (2008)
Published online: 12 October 2008 | doi:10.1038/nbt.1502
Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
Danwei Huangfu1, Kenji Osafune1,2, René Maehr1, Wenjun Guo3, Astrid Eijkelenboom1,4, Shuibing Chen1, Whitney Muhlestein1 & Douglas A Melton1
Abstract
Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor–induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical.
- Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
- ICORP Organ Regeneration Project, Japan Science and Technology Agency (JST), 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
- The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
- Biomedical Sciences, Utrecht University, The Netherlands.
Correspondence to: Douglas A Melton1 e-mail: dmelton@harvard.edu
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