Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells
Year: 2015
Type: article
Abstract: // Eugene Makarev 1, 2 , Kristen Fortney 1, 3 , Maria Litovchenko 4 , Karl H. Braunewell 5 , Alex Zhavoronkov 2, 6 , Anthony Atala 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 Correspondence to: Eugene Makarev, e-mail: [email protected] Anthony Atala, e-mail: [email protected] Keywords: Gerotarget, bioinformatics, algorithm, embryonic stem cells, pathway activation, iPSC Received: April 27, 2015 Accepted: August 10, 2015 Published: August 22, 2015 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.
Source: Oncotarget
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W1801220114