Cancer hallmarks in induced pluripotent cells: New insights

Sergey Malchenko, Vasiliy Galat, Elisabeth A. Seftor, Elio F. Vanin, Fabricio F. Costa, Richard E.B. Seftor, Marcelo B. Soares, Mary J.C. Hendrix

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)390-393
Number of pages4
JournalJournal of Cellular Physiology
Volume225
Issue number2
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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