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Completely erasing epigenetic marks

Completely erasing epigenetic marks

By Shubhankar Kulkarni on Jul 27, 2020

Question: How do we completely erase the epigenetic marks from the cells during reprogramming?

Direct reprogramming (avoiding dedifferentiation and redifferentiation) was shown to preserve the aging phenotype by increasing factors involved in cellular senescence (p53, p21, and p16).[1] [2] Examination of the iPSC methylome showed that they retain donor-age and tissue memory.[3] They have different teratogenic, hematopoietic, and osteogenic potential based on their tissue of origin. Certain CpG sites preserve age-specific methylation pattern even after 100 passages following reprogramming.[4] [5] These findings suggest that reprogramming does not fully bring differentiated cells to their ground state, but rather approximates it.

References

[1] Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, et al. Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects. Cell Stem Cell [Internet]. 2015 Dec;17(6):705–18. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1934590915004087

[2] Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, et al. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev [Internet]. 2009 Sep 15;23(18):2134–9. Available from: http://genesdev.cshlp.org/cgi/doi/10.1101/gad.1811609

[3] Lo Sardo V, Ferguson W, Erikson GA, Topol EJ, Baldwin KK, Torkamani A. Influence of donor age on induced pluripotent stem cells. Nat Biotechnol [Internet]. 2017 Jan 12;35(1):69–74. Available from: http://www.nature.com/articles/nbt.3749

[4] Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, et al. Epigenetic memory in induced pluripotent stem cells. Nature [Internet]. 2010 Sep 19;467(7313):285–90. Available from: http://www.nature.com/articles/nature09342

[5] Miura K, Okada Y, Aoi T, Okada A, Takahashi K, Okita K, et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol [Internet]. 2009 Aug 9;27(8):743–5. Available from: http://www.nature.com/articles/nbt.1554

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