Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells

被引：99

作者：

Yamaguchi, Shinpei

Kurimoto, Kazuki ^{[2
]}

Yabuta, Yukihiro ^{[2
]}

Sasaki, Hiroyuki ^{[3
]}

Nakatsuji, Norio ^{[4
,5
]}

Saitou, Mitinori ^{[2
]}

Tada, Takashi ^{[1
,6
]}

机构：

[1] Kyoto Univ, Lab Stem Cell Engn, Stem Cell Res Ctr, Inst Frontier Med Sci,Sakyo Ku, Kyoto 6068507, Japan

[2] RIKEN, Lab Mammalian Germ Cell Biol, Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan

[3] Res Org Informat & Syst, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan

[4] Kyoto Univ, Inst Frontier Med Sci, Sakyo Ku, Kyoto 6068507, Japan

[5] Kyoto Univ, Inst Integrated Cell Mat Sci iCeMS, Kyoto 6068501, Japan

[6] JST, CREST, Kawaguchi, Saitama 3320012, Japan

来源：

DEVELOPMENT | 2009年 / 136卷 / 23期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

Nanog; Knockdown; Primordial germ cell; Apoptosis; Mouse; EMBRYONIC STEM-CELLS; ES CELLS; RNA INTERFERENCE; CRE RECOMBINASE; SELF-RENEWAL; PLURIPOTENCY; GENE; EXPRESSION; OCT4; CLONING;

D O I：

10.1242/dev.041160

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The pluripotency factor Nanog is expressed in peri-implantation embryos and primordial germ cells (PGCs). Nanog-deficient mouse embryos die soon after implantation. To explore the function of Nanog in germ cells, Nanog RNA was conditionally knocked down in vivo by shRNA. Nanog shRNA transgenic (NRi-Tg) mice were generated through the formation of germline chimeras with NRi-Tg embryonic stem cells. In E12.5 Cre-induced ER-Cre/NRi-Tg and TNAP-Cre/NRi-Tg double-transgenic embryos, the number of alkaline phosphatase-positive and SSEA1-positive PGCs decreased significantly. In the E9.5 and E10.5 migrating Nanog-knockdown PGCs, TUNEL-positive apoptotic cell death became prominent in vivo and in vitro, despite Oct4 expression. Single-cell microarray analysis of E10.5 Nanog-knockdown PGCs revealed significant up- and downregulation of a substantial number of genes, including Tial1, Id1 and Suz12. These data suggest that Nanog plays a key role in the proliferation and survival of migrating PGCs as a safeguard of the PGC-specific molecular network.

引用

页码：4011 / 4020

页数：10

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