biostudies-literatureUnknown620(7975)Buckberry SCells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function^1-8. These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledNature863-872https://www.ebi.ac.uk/biostudies/studies/S-EPMC10447250biostudies-literatureTransient naive reprogramming corrects hiPS cells functionally and epigenetically.PMC10447250Polo JMLaslett ALFrazer TTan JPChen JLiu NOuyang JFRackham OJLde Mendoza ABreen JLister RLiu XVargas-Landin DBPoppe DChy HSNguyen TVFaulkner GJNefzger CMPaynter JMSun GPflueger JBuckberry SRossello FJSmits NfalseTransient naive reprogramming corrects hiPS cells functionally and epigenetically.Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function^1-8. These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowled2023-01-01T00:00:00Z2023 Aug2026-06-03T15:05:29.345Z2025-02-18T23:48:07.586ZS-EPMC104472503758733610.1038/s41586-023-06424-7