17 May 2005
A recent paper in Nature [Geijsen N et al. (2004) Nature 427, 148-153] reports the derivation of primordial mouse germ cell lines from embryonic stem cells. The group examined expression of specific genes involved in ES cell pluripotency and germ cell development (for instance, genes that are expressed in germ cells but not somatic cells) in embryoid bodies (EBs) formed from their ES cell lines over time. A rare population of differentiated EBs was identified that retained genetic markers of pluripotency, notably the surface antigen SSEA1. In order to establish whether this population comprised residual undifferentiated ES cells or primordial germ cells (PGCs), normal ES cells and cells from the EBs of interest were cultured separately for a week in the presence of retinoic acid, and resulting SSEA1+ cells were quantified. Retinoic acid causes rapid differentiation of ES cells but rapid proliferation of PGCs; in the treated ES cells, more than 99% lost expression of SSEA1 whereas 5-10% of the EB-derived cells retained SSEA1 expression.
The retinoic-acid resistant EB-derived cells were then analysed to determine whether they showed deletion of epigenetic imprints, a unique characteristic of PGCs. The methylation status of the DMR2 (differentially methylated region 2) of the Igf2r gene