Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in developing mouse epiblast
Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in developing mouse epiblast
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DOI：
10.1016/j.ydbio.2014.06.002
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发表时间：
2014-08-15
影响因子：
2.7
通讯作者：
Tada, Takashi
中科院分区：
文献类型：
--
作者：
Sun, Liang Tso;Yamaguchi, Shinpei;Tada, Takashi
Nanog是一种核心多能性因子，是稳定小鼠内细胞群（ICM）和胚胎干细胞（ESCs）多能性和原始生殖细胞存活所必需的。在这里，我们通过条件敲除（KD）、染色质免疫沉淀（ChIP）和体外与Nanog启动子的蛋白相互作用，研究了Nanog在刺激后小鼠胚胎外表皮细胞中的功能和调控。Nanog- kd外胚层的分化证明了Nanog在稳定多能性方面的作用。外胚层中Nanog的表达受Nodal/Smad2通路直接调控，并依赖于内脏内胚层。值得注意的是，Nanog启动子从ICM/ esc中的Oct4/Esrrb切换到外胚层中的Oct4/Smad2。Smad2直接与Oct4结合形成Nanog促进蛋白复合物。综上所述，这些数据表明Nanog在稳定由Nodal/Smad2信号介导的外胚层多能性中起着关键作用，这参与了早期发育胚胎中Nanog启动子的转换。(C) 2014爱思唯尔公司版权所有。
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. (C) 2014 Elsevier Inc. All rights reserved.