The histone demethylase KDM2B regulates human primordial germ cell-like cells specification.

Germline specification is a fundamental step for human reproduction and this biological phenomenon possesses technical challenges to study as it occurs immediately after blastocyst implantation. The establishment of human primordial germ cell-like cells (hPGCLCs) induction system allows sophisticated characterization of human primordial germ cells (hPGCs) development. However, the underlying molecular mechanisms of hPGCLC specification are not fully elucidated. Here, we observed particularly high expression of the histone demethylase in male fetal germ cells (FGCs) but not in male somatic cells. Besides, shared similar expression pattern with hPGC marker genes in hPGCLCs, suggesting an important role of in germ cell development. Although deletion of had no significant effects on human embryonic stem cell (hESC)'s pluripotency, loss of dramatically impaired hPGCLCs differentiation whereas ectopically expressed KDM2B could efficiently rescue such defect, indicating this defect was due to 's loss in hPGCLC specification. Mechanistically, as revealed by the transcriptional profiling, suppressed the expression of somatic genes thus inhibited somatic differentiation during hPGCLC specification. These data collectively indicate that KDM2B is an indispensable epigenetic regulator for hPGCLC specification, shedding lights on how epigenetic regulations orchestrate transcriptional events in hPGC development for future investigation.