Nanog is required for primitive endoderm formation through a non-cell autonomous mechanism
Nanog is required for primitive endoderm formation through a non-cell autonomous mechanism
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DOI：
10.1016/j.ydbio.2010.04.020
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发表时间：
2010-08-01
影响因子：
2.7
通讯作者：
Kemler, Rolf
中科院分区：
文献类型：
--
作者：
Messerschmidt, Daniel M.;Kemler, Rolf
小鼠发育早期的谱系分离导致CDX2或OCT4/NANOG阳性两种细胞群，CDX2阳性细胞形成滋养外胚层(TE)。Oct4/NANOG阳性细胞内细胞团(ICM)在第二个谱系中决定ICM细胞分离为上胚层(EPI)和原始内胚层(PE)，EPI和PE的形成取决于转录因子Nanog的活性和Gata4/6A对Nanog的作用。一个重要的多能性因素，在防止PE分化中被提出，因为突变的ICM的产物导致PE，而不是EPI衍生物。我们建立了Nanog突变小鼠系，并分析了EPI和PE在体内的形成。令人惊讶的是。在突变的ICM细胞中GATA4的表达缺失或强烈减少，因此Nanog的丢失不会导致早熟内胚层分化，然而，Nanog缺陷的胚胎保留了在嵌合胚胎中形成PE的能力，与最近的报告相反，在囊胚发育中，基于我们的发现，我们提出了一种非细胞自主的Nanog对正确的PE形成的要求，以及它在EPI测定(C)2010 Elsevier Inc.中的重要作用。
Early lineage segregation in mouse development results in two, either CDX2- or OCT4/NANOG-positive, cell populations CDX2-positive cells form the trophectoderm (TE). OCT4/NANOG-positive cells the inner cell mass (ICM) In a second lineage decision ICM cells segregate into Epiblast (EPI) and primitive endoderm (PE) EPI and PE formation depend on the activity of the transcription factors Nanog and Gata4/6 A role for Nanog. a crucial pluripotency factor, in preventing PE differentiation has been proposed, as outgrowths of mutant ICMs result in PE, but not EPI derivatives We established Nanog-mutant mouse lines and analyzed EPI and PE formation in vivo. Surprisingly. Gata4 expression in mutant ICM cells is absent or strongly decreased, thus loss of Nanog does not result in precocious endoderm differentiation However, Nanog-deficient embryos retain the capacity to form PE in chimeric embryos and, in contrast to recent reports, in blastocyst outgrowths Based on our findings we propose a non-cell autonomous requirement of Nanog for proper PE formation in addition to its essential role in EPI determination (C) 2010 Elsevier Inc. All rights reserved.