Niels Geijsen

Epigenetic control of gene expression limits the developmental potential of somatic cells. Successful reprogramming of the somatic cell nucleus is thought to depend on the release of this epigenetic information and is accompanied by robust DNA demethylation and changes in histone modification. We are interested in the molecular mechanisms underlying the maintenance and erasure of epigenetic memory.

Nuclear reprogramming occurs naturally in germ cells as part of their normal development and therefore the germ cell development is an elegant model system for the investigation of the molecular mechanisms orchestrating this process. We have developed a system in which germ cell differentiation can be studied in vitro. Upon aggregation of embryonic stem (ES) cells into structures called embryoid bodies (EBs), ES cells differentiate to form ectoderm, endoderm and mesoderm derivatives as well as germ cells. Although EBs lack the spatial features found in early embryos, the cellular microenvironment surrounding the developing germ cells resembles that found during early embryonic development.

We are now using this system to analyze the molecular factors that control germ cell development and reprogramming. By manipulating the developing germ cells, or the stromal microenvironment surrounding them, we can analyze the effect of a variety of genes on epigenetic events such as histone modification and DNA methylation.