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. 2018 Oct 2;9:4047. doi: 10.1038/s41467-018-06398-5

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© The Author(s) 2018

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. 5 — Age-related epigenetic signatures of iNSCs and PSC-derived NPCs. a Heatmap representation of DNAm levels at the 353 age-associated CpG sites derived from the Horvath model. The age-associated DNAm patterns of iNSCs differ from PSCs. b Age prediction using the Horvath model. Poly- and single-colony-derived low passage iNSC cultures (P ≤ 6) show a pronounced loss of age-related epigenetic signatures. Isogenic PB-iPSCs and iPSC-derived smNPCs display epigenetic age signatures similar to ESCs and ESC-derived NPCs. c Upon continuous expansion (P ≥ 18), a further decline of predicted DNAm age is observed using the Horvath model in 6 independent iNSC lines. Spontaneously differentiated cultures derived from 5 high passage iNSC lines and 3 isogenic high passage smNPC lines (P ≥ 18) show similar DNAm ages. d Subclones derived from single cells of a single-colony iNSC line (82b-3-SC) exhibit variable DNAm ages (Horvath model). N.D.: not determined