earticle

영어

Primordial germ cells (PGCs) are the embryonic precursors of mature gametes. In mice, primordial germ cells originate from lineage restricted precursors that are segregated from the undifferentiated epiblast. During the development of germ cells a remarkable epigenetic reprogramming takes place, which is thought to be essential for preventing the inheritance of epimutations in the offspring. Furthermore, PGC can be isolated and will convert into naïve pluripotent embryonic germ cells (EG) when cultured in vitro. These cells have the capacity to differentiate into all somatic tissues and generate germline chimeras efficiently. These features suggest that PGC could be an alternative source of pluripotent cells in large animals species, where establishment of pluripotent cell lines from preimplantation embryos has been very challenging. Our lab investigates the kinetics of germ cell development in the pig embryo and studies the signalling pathways involved in the generation of germ cell precursors from pluripotent cells. We find that pig PGCs undergo epigenetic reprogramming over an extended period of time during the migratory phase, involving the erasure of H3K9-me2 and acquisition of H3K27me3. This is also followed by extensive DNA demethylation and erasure of imprinted loci in cells arriving to the gonadal primordium. We have also established that BMP4 plays an important in inducing the germline in this species, as shown in human and mouse species. Having established the critical timepoints of germ cell establishment we are now developing protocols for the establishment of EG cell lines as well as working on the differentiation of pluripotent cells into in vitro gametes. A detailed study of the kinetics of germ cell ontogeny in the pig will inform into the conserved mechanisms of germ cell development in mammals and is of critical importance for developing safe technologies that will enable the generation of EG cell lines and in vitro gametes.