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

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Abstract

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.

Original languageEnglish
Pages (from-to)4011-4020
Number of pages10
JournalDevelopment
Volume136
Issue number23
DOIs
Publication statusPublished - Sep 25 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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    Yamaguchi, S., Kurimoto, K., Yabuta, Y., Sasaki, H., Nakatsuji, N., Saitou, M., & Tada, T. (2009). Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. Development, 136(23), 4011-4020. https://doi.org/10.1242/dev.041160