Meiotic Competent Human Germ Cell-like Cells Derived from Human Embryonic Stem Cells Induced by BMP4/WNT3A Signaling and OCT4/EpCAM (Epithelial Cell Adhesion Molecule) Selection

作者: Ching-Yu Chuang , Kuo-I Lin , Michael Hsiao , Lee Stone , Hsin-Fu Chen

DOI: 10.1074/JBC.M111.338434

关键词:

摘要: The establishment of an effective germ cell selection/enrichment platform from in vitro differentiating human embryonic stem cells (hESCs) is crucial for studying the molecular and signaling processes governing specification development. In this study, we developed a cell-enriching system that enables us to identify factors involved cell-fate induction hESCs vitro. First, demonstrated selection through OCT4-EGFP reporter can successfully increase percentage meiotic-competent, cell-like spontaneously hESCs. Furthermore, showed pluripotency associated surface marker, epithelial adhesion molecule (EpCAM), also expressed fetal gonads be used as marker enrichment Combining OCT4 EpCAM further enrich meiotic-competent population. Also, with OCT4+/EpCAM+ readout, synergistic effect BMP4/pSMAD1/5/8 WNT3A/β-CATENIN promoting toward germline fate. BMP4/WNT3A OCT4/EpCAM significantly putative population meiotic competency. Co-transplantation these dissociated mouse neonatal ovary into SCID mice resulted homogenous cluster formation vivo. stepwise established study provides useful tool elucidate mechanisms development, which has implications not only fertility research but regenerative medicine general.

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