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. 2020 Mar 5;11:1195. doi: 10.1038/s41467-020-14764-5

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 10 — 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.