Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells

Eugene Makarev, Kristen Fortney, Maria Litovchenko, Karl H. Braunewell, Alex Zhavoronkov, Anthony Atala

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Many attempts have been made to evaluate the safety and potency of human induced pluripotent stem cells (iPSCs) for clinical applications using transcriptome data, but results so far have been ambiguous or even contradictory. Here, we characterized stem cells at the pathway level, rather than at the gene level as has been the focus of previous work. We meta-analyzed publically-available gene expression data sets and evaluated signaling and metabolic pathway activation profiles for 20 human embryonic stem cell (ESC) lines, 12 human iPSC lines, five embryonic body lines, and six fibroblast cell lines. We demonstrated the close resemblance of iPSCs with ESCs at the pathway level, and provided examples of how pathway activity can be applied to identify iPSC line abnormalities or to predict in vitro differentiation potential. Our results indicate that pathway activation profiling is a promising strategy for evaluating the safety and potency of iPSC lines in translational medicine applications.

Original languageEnglish (US)
Pages (from-to)23204-23212
Number of pages9
JournalOncotarget
Volume6
Issue number27
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Cell Line
Safety
Translational Medical Research
Metabolic Networks and Pathways
Transcriptome
Stem Cells
Fibroblasts
Gene Expression
Genes

Keywords

  • Algorithm
  • Bioinformatics
  • Embryonic stem cells
  • Gerotarget
  • IPSC
  • Pathway activation

ASJC Scopus subject areas

  • Oncology

Cite this

Makarev, E., Fortney, K., Litovchenko, M., Braunewell, K. H., Zhavoronkov, A., & Atala, A. (2015). Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells. Oncotarget, 6(27), 23204-23212. https://doi.org/10.18632/oncotarget.4673

Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells. / Makarev, Eugene; Fortney, Kristen; Litovchenko, Maria; Braunewell, Karl H.; Zhavoronkov, Alex; Atala, Anthony.

In: Oncotarget, Vol. 6, No. 27, 2015, p. 23204-23212.

Research output: Contribution to journalArticle

Makarev, E, Fortney, K, Litovchenko, M, Braunewell, KH, Zhavoronkov, A & Atala, A 2015, 'Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells', Oncotarget, vol. 6, no. 27, pp. 23204-23212. https://doi.org/10.18632/oncotarget.4673
Makarev E, Fortney K, Litovchenko M, Braunewell KH, Zhavoronkov A, Atala A. Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells. Oncotarget. 2015;6(27):23204-23212. https://doi.org/10.18632/oncotarget.4673
Makarev, Eugene ; Fortney, Kristen ; Litovchenko, Maria ; Braunewell, Karl H. ; Zhavoronkov, Alex ; Atala, Anthony. / Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells. In: Oncotarget. 2015 ; Vol. 6, No. 27. pp. 23204-23212.
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