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 language | English |
|---|---|
| Pages (from-to) | 4011-4020 |
| Number of pages | 10 |
| Journal | Development |
| Volume | 136 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Sep 25 2009 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Developmental Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells
AU - Yamaguchi, Shinpei
AU - Kurimoto, Kazuki
AU - Yabuta, Yukihiro
AU - Sasaki, Hiroyuki
AU - Nakatsuji, Norio
AU - Saitou, Mitinori
AU - Tada, Takahashi
PY - 2009/9/25
Y1 - 2009/9/25
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=70450193267&partnerID=8YFLogxK
U2 - 10.1242/dev.041160
DO - 10.1242/dev.041160
M3 - Article
C2 - 19906868
AN - SCOPUS:70450193267
VL - 136
SP - 4011
EP - 4020
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 23
ER -