GSE232076 In vitro reconstitution of epigenetic reprogramming in the human germ line [RNA-Seq]

Contributors : Yusuke Murase ; Ryuta Yokogawa ; Yukihiro Yabuta ; Masahiro Nagano ; Yoshitaka Katou ; Manami Mizuyama ; Ayaka Kitamura ; Pimpitcha Puangsricharoen ; Chika Yamashiro ; Bo Hu ; Ken Mizuta ; Kosuke Ogata ; Yasushi Ishihama ; Mitinori SaitouSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensEpigenetic reprogramming resets parental epigenetic memories and differentiates primordial germ cells (PGCs) into mitotic pro-spermatogonia or oogonia, ensuring sexually dimorphic germ-cell development for totipotency. However, the mechanism of epigenetic reprogramming in humans remains unknown. Here, we establish a robust strategy for inducing epigenetic reprogramming and differentiation of pluripotent stem cell (PSC)-derived human PGC-like cells (hPGCLCs) into mitotic pro-spermatogonia or oogonia, coupled with their extensive amplification (~>10(10)-fold). Strikingly, bone morphogenetic protein (BMP) signaling is the key driver of these processes. Mechanistically, BMP signaling attenuates the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) pathway and both de novo and maintenance DNA methyltransferase (DNMT) activities, promoting replication-coupled, passive DNA demethylation. On the other hand, tens-eleven translocation (TET) 1, an active DNA demethylase abundant in human germ cells, plays a dual role in hPGCLC differentiation: safeguarding hPGCLCs against differentiation into amnion-like cells...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research