Reprogramming of human fibroblasts to pluripotency with lineage specifiers


  • Montserrat Nuria
  • Nivet Emmanuel
  • Sancho-Martinez Ignacio
  • Hishida Tomoaki
  • Kumar Sachin
  • Miquel Laia
  • Cortina Carme
  • Hishida Yuriko
  • Xia Yun
  • Esteban Concepcion Rodriguez
  • Izpisua Belmonte Juan Carlos


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


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.

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