Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2

Danwei Huangfu, Kenji Osafune, René Maehr, Wenjun Guo, Astrid Eijkelenboom, Shuibing Chen, Whitney Muhlestein, Douglas A. Melton

Research output: Contribution to journalArticlepeer-review

1054 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1269-1275
Number of pages7
JournalNature biotechnology
Volume26
Issue number11
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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