The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells
The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells
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DOI：
10.1016/s0092-8674(03)00393-3
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发表时间：
2003-05-30
期刊：
影响因子：
64.5
通讯作者：
Yamanaka, S
中科院分区：
文献类型：
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作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
源自囊胚内细胞团（ICM）的胚胎干细胞（ES细胞）在保持多能性的同时可无限增殖。白血病抑制因子（LIF）可通过激活Stat3维持小鼠ES细胞的自我更新。然而，LIF/Stat3对于维持ICM和人类ES细胞并非必需，这表明该通路对于多能性并非是根本性的。为了寻找一种对ICM和ES细胞多能性起关键作用的因子，我们进行了计算机差异显示分析，并鉴定出几个在小鼠ES细胞和着床前胚胎中特异性表达的基因。我们发现其中一个编码同源蛋白Nanog的基因能够不依赖LIF/Stat3维持ES细胞的自我更新。Nanog缺失的ICM无法形成上胚层，只能产生壁内胚层样细胞。Nanog缺失的ES细胞失去多能性并分化为胚外内胚层谱系。这些数据表明，Nanog是ICM和ES细胞多能性的关键因子。
Embryonic stem (ES) cells derived from the inner cell mass (ICM) of blastocysts grow infinitely while maintaining pluripotency. Leukemia inhibitory factor (LIF) can maintain self-renewal of mouse ES cells through activation of Stat3. However, LIF/Stat3 is dispensable for maintenance of ICM and human ES cells, suggesting that the pathway is not fundamental for pluripotency. In search of a critical factor(s) that underlies pluripotency in both ICM and ES cells, we performed in silico differential display and identified several genes specifically expressed in mouse ES cells and preimplantation embryos. We found that one of them, encoding the homeoprotein Nanog, was capable of maintaining ES cell self-renewal independently of LIF/Stat3. nanog-deficient ICM failed to generate epiblast and only produced parietal endoderm-like cells. nanog-deficient ES cells lost pluripotency and differentiated into extraembryonic endoderm lineage. These data demonstrate that Nanog is a critical factor underlying pluripotency in both ICM and ES cells.