It is still unclear how preimplantation embryos establish the totipotent cellular potential to develop a new life. Recent studies suggest DNA methylation reprogramming is essential for the formation of a toti- and pluripotent cell. We are studying epigenetic changes in the oocyte to embryo transition to identify key epigenetic factors and targets, which are impacting cellular potency at this fundamental stage of development.
Since the oocyte provides the vast majority of RNA and proteins vital for the beginning of life, this stage is the starting point for our analysis. We use the mouse as a standard model, which allows conducting functional studies by knockdown, overexpression and conditional/inducible knockout of epigenetic key factors. We combine single embryo/blastomere molecular methods to identify epigenetic marks and targets of epigenetic reprogramming and determine the ground state of totipotent mammalian chromatin in early embryogenesis in vivo.
Human pluripotent stem cells and induced pluripotent stem cells are of greatest interest for regenerative medicine, but so far available cell types have significant limitations. Genetic and epigenetic abnormalities of these cells compared to their in vivo counterpart in the embryo dampened the enthusiasm for the therapeutic use in personalized medicine. Understanding the embryo intrinsic establishment of cellular totipotency and its translation into the generation of totipotent cells presents an alternative solution for this use. Since the discovery of novel epigenome editing tools we are for the first time able to precisely modify epigenomic features and study their impact on cellular potency in vitro.
Epigenetic reprogramming during germ cell and early preimplantation development is characterized by global DNA methylation changes. Abnormal DNA methylation reprogramming during this sensitive period will not only affect the development of the affected growing germ cell and derived embryo, but also manifest in the transgenerational inheritance of the affected epigenome in subsequent generations. Environment and nutrition have been shown to affect epigenetic information. These observations are highlighting the significance of metabolic regulation of DNA methylation reprogramming for cell fate changes and disease development. We study the influence of metabolic changes on epigenetic reprogramming during early embryogenesis and the establishment of cellular potency, which will be beneficial for human reproductive medicine and the prevention of common human metabolic diseases like obesity or diabetes.