Induced pluripotency and oncogenic transformation are related processes

Stem Cells Dev. 2013 Jan 1;22(1):37-50. doi: 10.1089/scd.2012.0375. Epub 2012 Oct 26.


Induced pluripotent stem cells (iPSCs) have the potential for creating patient-specific regenerative medicine therapies, but the links between pluripotency and tumorigenicity raise important safety concerns. More specifically, the methods employed for the production of iPSCs and oncogenic foci (OF), a form of in vitro produced tumor cells, are surprisingly similar, raising potential concerns about iPSCs. To test the hypotheses that iPSCs and OF are related cell types and, more broadly, that the induction of pluripotency and tumorigenicity are related processes, we produced iPSCs and OF in parallel from common parental fibroblasts. When we compared the transcriptomes of these iPSCs and OF to their parental fibroblasts, similar transcriptional changes were observed in both iPSCs and OF. A significant number of genes repressed during the iPSC formation were also repressed in OF, including a large cohort of differentiation-associated genes. iPSCs and OF shared a limited number of genes that were upregulated relative to parental fibroblasts, but gene ontology analysis pointed toward monosaccharide metabolism as upregulated in both iPSCs and OF. iPSCs and OF were distinct in that only iPSCs activated a host of pluripotency-related genes, while OF activated cellular damage and specific metabolic pathways. We reprogrammed oncogenic foci (ROF) to produce iPSC-like cells, a process dependent on Nanog. However, the ROF had reduced differentiation potential compared to iPSC, suggesting that oncogenic transformation leads to cellular changes that impair complete reprogramming. Taken together, these findings support a model in which OF and iPSCs are related, yet distinct cell types, and in which induced pluripotency and induced tumorigenesis are similar processes.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Cell Differentiation / genetics*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Cells, Cultured
  • Coculture Techniques
  • Embryonic Stem Cells / pathology
  • Embryonic Stem Cells / physiology
  • Embryonic Stem Cells / transplantation
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibroblasts / physiology
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / pathology
  • Induced Pluripotent Stem Cells / physiology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms, Experimental / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-myc / physiology
  • Transcriptome


  • Antigens, Differentiation
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc