Abstract
Studies are beginning to emerge that demonstrate intriguing differences between humanโinduced 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 realโtime RTโPCR analyses reveal slightly lower levels of Nodal (a TGFโฮฒ family member) and Criptoโ1 (Nodal's coโreceptor) and a dramatic decrease in Lefty (Nodal's inhibitor and TGFโฮฒ 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 >10โfold 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: 390โ393, 2010. ยฉ 2010 WileyโLiss, Inc.