Epigenetic reprogramming in the germ cell lineage

The germ cell lineage is unique as it is the only cell lineage, which transmits genetic and epigenetic information from one generation to the next. In mammals, primordial germ cells (PGCs) are specified in the postimplantation embryo by instructive signals from extraembryonic tissues, whereafter they migrate into the genital ridges (future gonads, see Figure 4). During this time period PGCs undergo extensive epigenetic reprogramming. The reprogramming events can either act on a genome-wide level (histone modification changes, DNA-demethylation) or more locally (imprint erasure). X-chromosome reactivation in females encompasses several layers of epigenetic regulation (non-coding RNAs, histone modifications, DNA-methylation) and thereby serves as a model for epigenetic reprogramming in the germ line.

In our laboratory, we are studying epigenetic reprogramming in germ cells both during PGC development in vivo, but also by using in vitro germ cell derivation systems. The scalability of in vitro germ cell derivation allows us to address the X-reactivation process more mechanistically, than it would be possible in embryos only, from which only few cells can be obtained. Our goal is to discover, how X-reactivation in germ cells is regulated, how it is linked to the germ cell fate and if it is mechanistically similar or distinct from X-reactivation in other biological contexts.

Figure 4: Epigenetic reprogramming events during mouse germ cell (yellow) development. Some images have been reproduced from http://www.emouseatlas.org/ under a Creative Commons Attribution License.