Reprogramming of Human Somatic Cells to Pluripotency With Defined Factors

Nature. 2008 Jan 10;451(7175):141-6. doi: 10.1038/nature06534. Epub 2007 Dec 23.

Abstract

Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Differentiation
  • Cell Shape
  • Cells, Cultured
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Fetus / cytology
  • Fibroblasts / cytology
  • Gene Expression Profiling
  • HMGB Proteins / genetics
  • HMGB Proteins / metabolism*
  • Homeodomain Proteins / genetics
  • Humans
  • Infant, Newborn
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism*
  • Pluripotent Stem Cells / transplantation
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • SOXB1 Transcription Factors
  • Teratoma / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transplantation, Heterologous

Substances

  • DNA-Binding Proteins
  • GKLF protein
  • HMGB Proteins
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • MYC protein, human
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factors