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

Research output: Contribution to journalArticle

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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

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Germ Cells
Cell Death
Small Interfering RNA
Embryonic Structures
Tissue Array Analysis
Single-Cell Analysis
In Situ Nick-End Labeling
Embryonic Stem Cells
Alkaline Phosphatase
Up-Regulation
Down-Regulation
RNA
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

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

Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. / Yamaguchi, Shinpei; Kurimoto, Kazuki; Yabuta, Yukihiro; Sasaki, Hiroyuki; Nakatsuji, Norio; Saitou, Mitinori; Tada, Takahashi.

In: Development, Vol. 136, No. 23, 25.09.2009, p. 4011-4020.

Research output: Contribution to journalArticle

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, vol. 136, no. 23, pp. 4011-4020. https://doi.org/10.1242/dev.041160
Yamaguchi, Shinpei ; Kurimoto, Kazuki ; Yabuta, Yukihiro ; Sasaki, Hiroyuki ; Nakatsuji, Norio ; Saitou, Mitinori ; Tada, Takahashi. / Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. In: Development. 2009 ; Vol. 136, No. 23. pp. 4011-4020.
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