DNA Methylation; Embryo, Mammalian; Embryonic Stem Cells; Epigenomics
In early mammalian development, a little miracle is happening with every start of a new life. Here, shortly after fertilization, mammalian embryogenesis is characterized by dramatic epigenetic remodeling of the oocyte and sperm chromatin. This epigenetic reprogramming of the highly specialized egg and sperm epigenomes gives rise to the toti- and pluripotent blastomeres of preimplantation embryos, which are capable of generating all cell types needed to form a new life. Most intriguingly, the genomes of early embryos undergo genome-wide DNA methylation (5-methyl-cytosine, 5mC) changes. Recent work suggests that DNA methylation reprogramming is an essential mechanism in early embryogenesis and the establishment of toti- and pluripotency.
Our group aims to elucidate the embryo intrinsic epigenetic reprogramming that drives early preimplantation development and the establishment of cellular potency. We seek to understand the influence of epigenetic reprogramming on the establishment of toti-/pluripotency in vivo. Insights from epigenomic changes in early embryogenesis in vivo will identify key factors for the generation of toti- and pluripotent cells in vitro, which will translate into the improved generation of human stem cells for regenerative medicine and treatment of common human diseases.
Techniques, methods & infrastructure
We use mouse embryos and embryonic stem cells in combination with novel epigenomic editing methods to investigate the impact of epigenetic changes and inter-/transgenerational inheritance of epimutations on development and cellular potency.
- Srinivasan, R. et al., 2020. Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage. Science Advances, 6(12), p.eaaz9115. Available at: http://dx.doi.org/10.1126/sciadv.aaz9115.
- Durruthy-Durruthy, J. et al., 2016. Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency. Developmental Cell, 38(1), pp.100-115. Available at: http://dx.doi.org/10.1016/j.devcel.2016.06.014.
- Wossidlo, M. et al., 2011. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nature Communications, 2, p.241. Available at: http://dx.doi.org/10.1038/ncomms1240.
- Wossidlo, M. et al., 2010. Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes. The EMBO Journal, 29(11), pp.1877-1888. Available at: http://dx.doi.org/10.1038/emboj.2010.80.