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

First Author  Yamaguchi S Year  2009
Journal  Development Volume  136
Issue  23 Pages  4011-20
PubMed ID  19906868 Mgi Jnum  J:154977
Mgi Id  MGI:4412109 Doi  10.1242/dev.041160
Citation  Yamaguchi S, et al. (2009) Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. Development 136(23):4011-20
abstractText  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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