Pluripotential competence of cells associated with Nanog activity

Pluripotential competence of cells associated with Nanog activity
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DOI:
10.1016/j.mod.2004.08.008
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发表时间:
2005-01-01
影响因子:
2.6
通讯作者:
Tada, T
Tada, T
中科院分区:
生物学4区
文献类型:
--
作者:
Hatano, S;Tada, M;Tada, T

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Nanog是一种新型的多能细胞特异性基因,在维持早期、植入后胚胎和胚胎干细胞(ES)的未分化状态中起着至关重要的作用。我们已经探索了Nanog和Nanog同源物的表达模式和功能。Nanog-ps1定位于7号染色体上,是一个假基因。体内免疫细胞化学分析表明,NANOG蛋白在未受精卵母细胞中不表达,在桑椹胚细胞、囊胚内细胞团、E6.5和E7.5胚胎的上胚层中表达,而在植入后早期胚胎的原始生殖细胞中不表达。在猴子和人类胚胎干细胞中。NANOG表达仅限于未分化细胞。此外,体细胞来源的Nanog的再激活与细胞与ES细胞杂交和核移植到去核卵母细胞中诱导的核重编程紧密相关。值得注意。小鼠Nanog(+/-)ES细胞。其产生的NANOG量约为野生型ES细胞产生的NANOG量的一半。在包括LIF的培养基中容易分化为多谱系细胞。外源Nanog的组成型表达完全挽救了不稳定的未分化状态。因此,Nanog的活性与细胞的未分化状态密切相关,即使在核重编程体细胞中也是如此。Nanog可以作为一个关键的调节器,以剂量依赖性的方式维持多能性。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Nanog is a novel pluripotential cell-specific gene that plays a crucial role in maintaining the undifferentiated state of early, postimplantation embryos and embryonic stem (ES) cells. We have explored the expression pattern and function of Nanog and a Nanog-homologue. Nanog-ps1.Nanog-ps1 was mapped on Chromosome 7 and shown to be a pseudogene. Immunocytochemical analysis in vivo Showed that the NANOG protein was absent in unfertilized oocytes, and was detected in cells of morula-stage embryos, the inner cell mass of blastocysts and the epiblast of E6.5 and E7.5 embryos, but not in primordial germ cells of early postimplantation embryos. In monkey and human ES cells. NANOG expression was restricted to undifferentiated cells. Furthermore, reactivation of the somatic cell-derived Nanog was tightly linked with nuclear reprogramming induced by cell hybridization with ES cells and by nuclear transplantation into enucleated oocyte. Notably. mouse Nanog (+/-) ES cells. which produced approximately half the amount of NANOG produced by wild-type ES cells. readily differentiated to multi-lineage cells in culture medium including LIF. The labile undifferentiated state was fully rescued by constitutive expression of exogenous Nanog. Thus, the activity of Nanog is tightly correlated with an undifferentiated state of cells even in nuclear reprogrammed somatic cells. Nanog may function as a key regulator for sustaining pluripotency in a dose-dependent manner. (C) 2004 Elsevier Ireland Ltd. All rights reserved.