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

生殖系来源的多能干细胞神经分化过程中印迹基因的表观遗传改变

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作者:Hye Jeong Lee, Na Young Choi, Seung-Won Lee, Kisung Ko, Tae Sook Hwang, Dong Wook Han, Jisun Lim, Hans R Schöler, Kinarm Ko

Abstract

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 in vitro neural differentiation model to investigate whether the imprinting patterns are maintained or altered during differentiation. The androgenetic patterns of H19, Snrpn, and Mest were maintained even after differentiation of gPS cells into NSCs (gPS-NSCs), whereas the fully unmethylated status of Ndn 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.

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