@article{6d38c37da72946b8a9d000e456a7fdb3,
title = "SOX17 is a critical specifier of human primordial germ cell fate",
abstract = "Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.",
author = "Naoko Irie and Leehee Weinberger and Tang, \{Walfred W.C.\} and Toshihiro Kobayashi and Sergey Viukov and Manor, \{Yair S.\} and Sabine Dietmann and Hanna, \{Jacob H.\} and Surani, \{M. Azim\}",
note = "JSPS; BIRAX (the Britain Israel Research and Academic Exchange Partnership) initiative; ERC [StG-2011-281906]; Helmsley Charitable Trust; ISF (Bikura, Morasha, ICORE); ICRF; Abisch Frenkel Foundation; Fritz Thyssen Stiftung; Erica and Robert Drake; Benoziyo Endowment fund; Flight Attendant Medical Research Institute (FAMRI); New York Stem Cell Foundation; Croucher Foundation and Cambridge Trust; HFSP; Wellcome TrustWe thank Rick Livesey and his lab for help with the culture of hESCs; Sohei Kitazawa and Janet Shipley for the TCam-2 cells; Nigel Miller and Andy Riddell for cell sorting, Roger Barker, Xiaoling He, and Pam Tyers for collection of human embryos; and Charles Bradshaw for help with bioinformatics. We thank members of the Surani and Hanna labs for important discussions and technical help. N.I. is supported by Grant-in-Aid for fellows of the JSPS and by BIRAX (the Britain Israel Research and Academic Exchange Partnership) initiative, who provided a project grant to J.H.H. and M.A.S. J.H.H. is supported by Ilana and Pascal Mantoux, the Kimmel Award, ERC (StG-2011-281906), Helmsley Charitable Trust, ISF (Bikura, Morasha, ICORE), ICRF, the Abisch Frenkel Foundation, the Fritz Thyssen Stiftung, Erica and Robert Drake, Benoziyo Endowment fund, and the Flight Attendant Medical Research Institute (FAMRI). J.H.H. is a New York Stem Cell Foundation Robertson Investigator. W.C.C.T. is supported by Croucher Foundation and Cambridge Trust; M.A.S. is supported by HFSP and a Wellcome Trust Investigator Award.",
year = "2015",
month = jan,
day = "15",
doi = "10.1016/j.cell.2014.12.013",
language = "الإنجليزيّة",
volume = "160",
pages = "253--268",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "1-2",
}