Team Presents Reprogramming Strategy Informed by Epigenetic Dynamics

In Nature, researchers from Monash University, the University of Western Australia, and elsewhere describe a cellular reprogramming strategy that appears to bring the functional and epigenetic profiles found in human induced pluripotent stem cells (iPSCs) closer to those described in human embryonic stem cells. With the help of whole-genome bisulfite sequencing and RNA sequencing, the team tracked DNA methylation and gene expression profiles during somatic cell reprogramming with methods that produce "primed" iPSCs similar to epiblast cells after implantation, comparing them with strategies that produce iPSCs in a "naïve" state more similar to pre-implantation epiblast cells. "These two reprogramming paradigms provide tractable model systems to study how epigenome resetting is influenced by environments resembling distinct developmental states of pluripotency," the authors explain, noting that their results suggest epigenetic alterations "emerge midway through primed reprogramming, whereas DNA demethylation begins early in naïve reprogramming." The findings prompted them to come up with a method known as "transient-naïve-treatment" that takes these methylation dynamics into account and "emulates the embryonic epigenetic reset."