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

Nat Biotechnol. 2008 Nov;26(11):1269-75. doi: 10.1038/nbt.1502. Epub 2008 Oct 12.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotechnology / methods
  • Cell Differentiation
  • Cells, Cultured
  • Cellular Reprogramming* / drug effects
  • Culture Media
  • Embryonic Stem Cells / cytology
  • Epigenesis, Genetic
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Humans
  • Mice
  • Octamer Transcription Factor-3 / metabolism*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • SOXB1 Transcription Factors / metabolism*
  • Valproic Acid / pharmacology*

Substances

  • Culture Media
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Valproic Acid