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

Shinpei Yamaguchi, Kazuki Kurimoto, Yukihiro Yabuta, Hiroyuki Sasaki, Norio Nakatsuji, Mitinori Saitou, Takahashi Tada

研究成果: Contribution to journalArticle査読

100 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)4011-4020
ページ数10
ジャーナルDevelopment
136
23
DOI
出版ステータス出版済み - 9 25 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学

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