SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

被引：627

作者：

Irie, Naoko ^{[1
,2
,3
]}

Weinberger, Leehee ^{[4
]}

Tang, Walfred W. C. ^{[1
,2
,3
]}

Kobayashi, Toshihiro ^{[1
,2
,3
]}

Viukov, Sergey ^{[4
]}

Manor, Yair S. ^{[4
]}

Dietmann, Sabine ^{[3
]}

Hanna, Jacob H. ^{[4
]}

Surani, M. Azim ^{[1
,2
,3
]}

机构：

[1] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England

[2] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England

[3] Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 3EG, England

[4] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

来源：

CELL | 2015年 / 160卷 / 1-2期

基金：

英国惠康基金;

关键词：

EMBRYONIC STEM-CELLS; NAIVE PLURIPOTENCY; DNA DEMETHYLATION; GROUND-STATE; SELF-RENEWAL; IN-VITRO; MOUSE; SPECIFICATION; MICE; DIFFERENTIATION;

D O I：

10.1016/j.cell.2014.12.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：253 / 268

页数：16

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