Makarev Eugene, Fortney Kristen, Litovchenko Maria, Braunewell Karl H, Zhavoronkov Alex, Atala Anthony
Atlas Regeneration, Inc, Winston-Salem, NC, USA.
Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD, USA.
Oncotarget. 2015 Sep 15;6(27):23204-12. doi: 10.18632/oncotarget.4673.
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.
人们已经进行了许多尝试，利用转录组数据评估人类诱导多能干细胞（iPSC）用于临床应用的安全性和效力，但迄今为止的结果尚不明确，甚至相互矛盾。在这里，我们在通路水平而非基因水平对干细胞进行了表征，而基因水平一直是以往研究的重点。我们对公开可用的基因表达数据集进行了荟萃分析，并评估了20个人类胚胎干细胞（ESC）系、12个人类iPSC系、5个胚状体系和6个成纤维细胞系的信号传导和代谢通路激活谱。我们证明了iPSC在通路水平上与ESC非常相似，并提供了一些示例，说明通路活性如何可用于识别iPSC系异常或预测体外分化潜能。我们的结果表明，通路激活分析是评估iPSC系在转化医学应用中的安全性和效力的一种有前景的策略。
