Principles and programming of the mammalian germ line. (360G-Wellcome-096738_Z_11_Z)

Germ cells exhibit unique and comprehensive erasure and re-establishment ofepigenetic information, which is critical for totipotency and the transmission of geneticand epigenetic information with long-term consequences for subsequent generations1.The principles of germline biology have the potential to provide core knowledge for thecontrol and manipulation of cell fates in developing and diseased tissues.A clear understanding of the transient state of competence is required first, together withhow these primed cells respond specifically to the critical regulators of mouse primordialgerm cell (PGC) specification. Importantly, with germ cells we also have a uniqueopportunity to identify and understand how epigenetic regulators can systematicallyreset the epigenome, even of the somatic nuclei when exposed in oocytes.Understandably, we know least about the largely inaccessible early human germ cells(hPGC), but we have opportunities to establish credible in vitro models through inductionof competence in pluripotent and induced stem cells (hESC and hiPS) for the generationand systematic studies of hPGCs.Accumulation of genome scale information on early mammalian germ cells mightimprove the prospects for the integration and modelling of dynamic changes regulatingkey germline properties, and allow testable predictions about the performance of thiscrucial lineage. This may also help to build experimental models that mimic keygermline properties and through this, a route to the experimental manipulation of cellfates and physiology.