Efficient and Rapid Generation of Induced Pluripotent Stem Cells From Human Keratinocytes

Nat Biotechnol. 2008 Nov;26(11):1276-84. doi: 10.1038/nbt.1503. Epub 2008 Oct 17.

Abstract

The utility of induced pluripotent stem (iPS) cells for investigating the molecular logic of pluripotency and for eventual clinical application is limited by the low efficiency of current methods for reprogramming. Here we show that reprogramming of juvenile human primary keratinocytes by retroviral transduction with OCT4, SOX2, KLF4 and c-MYC is at least 100-fold more efficient and twofold faster compared with reprogramming of human fibroblasts. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, global gene expression profiles and differentiation potential in vitro and in vivo. To underscore the efficiency and practicability of this technology, we generated KiPS cells from single adult human hairs. Our findings provide an experimental model for investigating the bases of cellular reprogramming and highlight potential advantages of using keratinocytes to generate patient-specific iPS cells.

Publication types

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

MeSH terms

  • Adult
  • Biotechnology / methods
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cellular Reprogramming
  • Child, Preschool
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Octamer Transcription Factor-3 / genetics
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Retroviridae / genetics
  • SOXB1 Transcription Factors / genetics
  • Time Factors
  • Transduction, Genetic

Substances

  • GKLF protein
  • Kruppel-Like Transcription Factors
  • MYC protein, human
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • SOX2 protein, human
  • SOXB1 Transcription Factors