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Publication : Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in developing mouse epiblast.

First Author  Sun LT Year  2014
Journal  Dev Biol Volume  392
Issue  2 Pages  182-92
PubMed ID  24929238 Mgi Jnum  J:214985
Mgi Id  MGI:5604323 Doi  10.1016/j.ydbio.2014.06.002
Citation  Sun LT, et al. (2014) Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in developing mouse epiblast. Dev Biol 392(2):182-92
abstractText  Nanog, a core pluripotency factor, is required for stabilizing pluripotency of inner cell mass (ICM) and embryonic stem cells (ESCs), and survival of primordial germ cells in mice. Here, we have addressed function and regulation of Nanog in epiblasts of postimplantation mouse embryos by conditional knockdown (KD), chromatin immunoprecipitation (ChIP) using in vivo epiblasts, and protein interaction with the Nanog promoter in vitro. Differentiation of Nanog-KD epiblasts demonstrated requirement for Nanog in stabilization of pluripotency. Nanog expression in epiblast is directly regulated by Nodal/Smad2 pathway in a visceral endoderm-dependent manner. Notably, Nanog promoters switch from Oct4/Esrrb in ICM/ESCs to Oct4/Smad2 in epiblasts. Smad2 directly associates with Oct4 to form Nanog promoting protein complex. Collectively, these data demonstrate that Nanog plays a key role in stabilizing Epiblast pluripotency mediated by Nodal/Smad2 signaling, which is involved in Nanog promoter switching in early developing embryos.
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