TY - JOUR
T1 - SOX17 is a critical specifier of human primordial germ cell fate
AU - Irie, Naoko
AU - Weinberger, Leehee
AU - Tang, Walfred W.C.
AU - Kobayashi, Toshihiro
AU - Viukov, Sergey
AU - Manor, Yair S.
AU - Dietmann, Sabine
AU - Hanna, Jacob H.
AU - Surani, M. Azim
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/1/15
Y1 - 2015/1/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84920989095
UR - https://www.scopus.com/pages/publications/84920989095#tab=citedBy
U2 - 10.1016/j.cell.2014.12.013
DO - 10.1016/j.cell.2014.12.013
M3 - Article
C2 - 25543152
AN - SCOPUS:84920989095
SN - 0092-8674
VL - 160
SP - 253
EP - 268
JO - Cell
JF - Cell
IS - 1-2
ER -