Genetically unmatched human iPSC and ESC exhibit equivalent gene expression and neuronal differentiation potential

The potential uniformity between differentiation and therapeutic potential of human embryonic stemcells (hESCs) and human induced pluripotent stem cells (hiPSCs) remains debatable. We studied thegene expression profiles, pathways analysis and the ability to differentiated into neural progenitorcells (NPCs) and motor neurons (MNs) of genetically unmatched integration-free hiPSC versus hESCto highlight possible differences/similarities between them at the molecular level. We also providedthe functional information of the neurons derived from the different hESCs and hiPSCs lines using theNeural Muscular Junction (NMJ) Assay. The hiPSC line was generated by transfecting human epidermalfibroblasts (HEF) with episomal DNAs expressing Oct4, Sox2, Klf4, Nanog, L-Myc and shRNA againstp53. For the hESCs line, we used the NIH-approved H9 cell line. Using unsupervised clustering bothhESCs and hiPSCs were clustered together implying homogeneous genetic states. The genetic profilesof hiPSCs and hESCs were clearly similar but not identical. Collectively, our data indicate close molecularsimilarities between genetically unmatched hESCs and hiPS in term of gene expression, and signalingpathways. Moreover, both cell types exhibited similar cholinergic motor neurons differentiationpotential with marked ability of the differentiated hESCs and hiPSCs-derived MNs to induce contractionof myotubes after 4 days of co-culture.