Pluto Bioinformatics

GSE147498: Long-term expansion with germline potential of human primordial germ cell-like cells in vitro [RNA-seq]

Bulk RNA sequencing

Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ celllike cells (hPGCLCs) derived from humaninduced pluripotent stem cells (hiPSCs) can be propagated to at least ~10^6fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGClike transcriptome and preserve their genomewide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50fold) and persist only around 1 week, yet undergo cellautonomous genomewide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneicreconstituted ovaries, expanded hPGCLCs initiate genomewide DNA demethylation and differentiate into oogonia/gonocytelike cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage. SOURCE: Yukihiro Yabuta (yabyab@anat2.med.kyoto-u.ac.jp) - Kyoto University, Graduate school of medicine