Cancer hallmarks in induced pluripotent cells: new insights.
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-beta family member) and Cripto-1 (Nodal's co-receptor) and a dramatic decrease in Lefty (Nodal's inhibitor and TGF-beta 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..
Malchenko
Sergey
S
Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60614, USA.
Galat
Vasiliy
V
Seftor
Elisabeth A
EA
Vanin
Elio F
EF
Costa
Fabricio F
FF
Seftor
Richard E B
RE
Soares
Marcelo B
MB
Hendrix
Mary J C
MJ
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger