Epigenetic alteration of imprinted genes during neural differentiation of germline-derived pluripotent stem cells

Spermatogonial stem cells (SSCs), which are unipotent stem cells in the testes that give rise to sperm, can be converted into germline-derived pluripotent stem (gPS) by self-induction. The androgenetic imprinting pattern of SSCs is maintained even after their reprogramming into gPS cells. In this study, we used an <i>in vitro</i> neural differentiation model to investigate whether the imprinting patterns are maintained or altered during differentiation. The androgenetic patterns of <i>H19, Snrpn</i>, and <i>Mest</i> were maintained even after differentiation of gPS cells into NSCs (gPS-NSCs), whereas the fully unmethylated status of <i>Ndn</i> in SSCs was altered to somatic patterns in gPS cells and gPS-NSCs. Thus, our study demonstrates epigenetic alteration of genomic imprinting during the induction of pluripotency in SSCs and neural differentiation, suggesting that gPS-NSCs can be a useful model to study the roles of imprinted genes in brain development and human neurodevelopmental disorders.