Cancer hallmarks in induced pluripotent cells: New insights

Authors

  • Sergey Malchenko,

    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Vasiliy Galat,

    1. Developmental Biology Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Elisabeth A. Seftor,

    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Elio F. Vanin,

    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Fabricio F. Costa,

    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Richard E.B. Seftor,

    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Marcelo B. Soares,

    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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  • Mary J.C. Hendrix

    Corresponding author
    1. Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
    • Children's Memorial Research Center, 2430 N. Halsted St., Chicago, IL 60614.
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  • Sergey Malchenko and Vasiliy Galat contributed equally to this study as first authors.

Abstract

Studies are beginning to emerge that demonstrate intriguing differences between human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Here, we investigated the expression of key members of the Nodal embryonic signaling pathway, critical to the maintenance of pluripotency in hESCs. Western blot and real-time RT-PCR analyses reveal slightly lower levels of Nodal (a TGF-β family member) and Cripto-1 (Nodal's co-receptor) and a dramatic decrease in Lefty (Nodal's inhibitor and TGF-β family member) in hiPSCs compared with hESCs. The noteworthy drop in hiPSC's Lefty expression correlated with an increase in the methylation of Lefty B CpG island. Based on these findings, we addressed a more fundamental question related to the consequences of epigenetically reprogramming hiPSCs, especially with respect to maintaining a stable ESC phenotype. A global comparative analysis of 365 microRNAs (miRs) in two hiPSC versus four hESC lines ultimately identified 10 highly expressed miRs in hiPCSs with >10-fold difference, which have been shown to be cancer related. These data demonstrate cancer hallmarks expressed by hiPSCs, which will require further assessment for their impact on future therapies. J. Cell. Physiol. 225: 390–393, 2010. © 2010 Wiley-Liss, Inc.

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