Written and published by Biogerontology Research Foundation staff in collaboration with Stanford University Medical Center (Department of Developmental Biology), Ludwig Maximilian University of Munich (Department of Computational Genomics), Ruhr University Bochum (Department of Neurophysiology), Atlas Regeneration, Inc,., and Insilico Medicine, Inc.
Makarev E(1,2), Fortney K(1,3), Litovchenko M(4), Braunewell KH(5), Zhavoronkov A(2,6), Atala A(1,7).
(1) Atlas Regeneration, Inc, Winston-Salem, NC, USA.
(2) Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD, USA.
(3) Department of Developmental Biology, Stanford University Medical Center, Stanford, CA, USA.
(4) Department of Computational Genomics, Ludwig Maximilian University of Munich, Germany.
(5) Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Germany.
(6) The Biogerontology Research Foundation, London, UK.
(7) Department of Urology, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
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.