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Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity

View ORCID ProfileNelly Olova, Daniel J Simpson, Riccardo Marioni, View ORCID ProfileTamir Chandra
doi: https://doi.org/10.1101/292680
Nelly Olova
1MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;
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Daniel J Simpson
1MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;
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Riccardo Marioni
2Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom;
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Tamir Chandra
1MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;
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Abstract

Induced pluripotent stem cells (IPSCs), with their unlimited regenerative capacity, carry the promise for tissue replacement to counter age-related decline. However, attempts to realise in vivo iPSC have invariably resulted in the formation of teratomas. Partial reprogramming in prematurely aged mice has shown promising results in alleviating age-related symptoms without teratoma formation. Does partial reprogramming lead to rejuvenation (i.e. “younger” cells), rather than dedifferentiation, which bears the risk of cancer? Here we analyse cellular age during iPSC reprogramming and find that partial reprogramming leads to a reduction in the biological age of cells. We also find that the loss of somatic gene expression and epigenetic age follow different kinetics, suggesting that rejuvenation can be achieved with a minimised risk of cancer.

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Posted March 31, 2018.
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Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity
Nelly Olova, Daniel J Simpson, Riccardo Marioni, Tamir Chandra
bioRxiv 292680; doi: https://doi.org/10.1101/292680
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Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity
Nelly Olova, Daniel J Simpson, Riccardo Marioni, Tamir Chandra
bioRxiv 292680; doi: https://doi.org/10.1101/292680

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