Fig. 10: Epigenetic model for improvement of multi-lineage differentiation by reversion of primed hiPSC to a naïve pluripotent state.

a Waddington landscape model70 for the epigenetic barriers posed by lineage priming, incomplete reprogramming, and disease-associated epigenetic aberrations in primed hiPSC (blue). These obstacles may be overcome with molecular reversion to a tankyrase/PARP inhibitor-regulated naïve epiblast-like state (red) possessing a developmentally naïve epigenetic configuration. b Compared to lineage-primed DhiPSC, N-DhiPSC possessed a de-repressed naïve epiblast-like epigenetic configuration at bivalent PRC2-regulated developmental promoters that was highly poised for non-biased, multi-lineage lineage specification.