Details

Autor(en) / Beteiligte

• Irie, Naoko
• Weinberger, Leehee
• Tang, Walfred W.C.
• Kobayashi, Toshihiro
• Viukov, Sergey
• Manor, Yair S.
• Dietmann, Sabine
• Hanna, Jacob H.
• Surani, M. Azim

Titel

SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

Ist Teil von

• Cell, 2015-01, Vol.160 (1-2), p.253-268

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •A defined model for hPGCLC specification from germline-competent hESCs•Expression profiles of hPGCLCs match with authentic hPGCs•SOX17 is the key regulator of hPGCLC•CD38 glycoprotein is a cell-surface marker of the human germline Different from that in mice, SOX17 is the key regulator for human primordial germ cell specification, suggesting fundamental differences between early mouse and human development.