Epigenetic blind spots - the role of DNA methylation dynamics in stem cell-based models of embryogenesis

Embryo-like structures, or stembryos, complement embryo research in innovative ways and provide an alternative when embryo utilization is ethically or technically limited. These models, however, are hindered by experimental variability and limited developmental potential, whose causes are still not fully understood. Establishment of appropriate DNA methylation patterns is crucial for mammalian development but characterization of DNA methylation in stembryo models has been largely overlooked. This Perspective manuscript highlights this knowledge gap and suggests that characterization of DNA methylation, and in the future also of other epigenetic modifications, should become standard practice in stembryo model characterization. Available datasets indicate that differences in DNA methyltransferase expression between stembryos and embryos exist, thus suggesting an avenue of investigation to further improve these models.