Reprogramming of human fibroblasts to pluripotency with lineage specifiers

Cell Stem Cell. 2013 Sep 5;13(3):341-50. doi: 10.1016/j.stem.2013.06.019. Epub 2013 Jul 18.

Abstract

Since the initial discovery that OCT4, SOX2, KLF4, and c-MYC overexpression sufficed for the induction of pluripotency in somatic cells, methodologies replacing the original factors have enhanced our understanding of the reprogramming process. However, unlike in mouse, OCT4 has not been replaced successfully during reprogramming of human cells. Here we report on a strategy to accomplish this replacement. Through a combination of transcriptome and bioinformatic analysis we have identified factors previously characterized as being lineage specifiers that are able to replace OCT4 and SOX2 in the reprogramming of human fibroblasts. Our results show that it is possible to replace OCT4 and SOX2 simultaneously with alternative lineage specifiers in the reprogramming of human cells. At a broader level, they also support a model in which counteracting lineage specification networks underlies the induction of pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Dedifferentiation* / genetics
  • Cell Lineage
  • Cells, Cultured
  • Computational Biology / methods
  • Fibroblasts / physiology*
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Guided Tissue Regeneration
  • Humans
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Pluripotent Stem Cells / physiology*
  • RNA, Small Interfering / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transgenes / genetics

Substances

  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse

Associated data

  • GEO/GSE48275