Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages
Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages
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DOI：
10.1634/stemcells.2005-0080
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发表时间：
2005-09-01
期刊：
影响因子：
5.2
通讯作者：
Lako, M
中科院分区：
文献类型：
--
作者：
Hyslop, L;Stojkovic, M;Lako, M
同源盒转录因子Nanog被认为在维持海洋胚胎干细胞的未分化状态中起着至关重要的作用。人类的对应体NANOG已被确定，但其功能和定位迄今尚未描述。我们采用RNA干扰和实时定量聚合酶链反应相结合的方法研究了人胚胎干细胞和胚胎癌细胞的NANOG。转染NANOG特异性小干扰rna降低NANOG转录物和蛋白水平，诱导胚胎外内胚层相关基因GATA4、GATA6、层粘连蛋白B1和AFP的激活，以及滋养外胚层相关基因CDX2、GATA2、hcg - α和hcg - β的上调。人胚胎着床前的免疫染色显示，NANOG在膨大囊胚的内细胞团中表达，而在早期胚胎中不表达，这与维持多能性的作用一致。综上所述，我们的研究结果表明，NANOG通过阻止人类胚胎干细胞和癌细胞分化为胚胎外胚层和滋养外胚层谱系，充当了多能性的守门人。
The homeobox transcription factor Nanog has been proposed to play a crucial role in the maintenance of the undifferentiated state of marine embryonic stem cells. A human counterpart, NANOG, has been identified, but its function and localization have not hitherto been described. We have used a combination of RNA interference and quantitative real-time polymerase chain reaction to study NANOG in human embryonic stem and embryonic carcinoma cells. Transfection of NANOG-specific small interfering RNAs reduced levels of NANOG transcript and protein and induced activation of the extraembryonic endoderm-associated genes GATA4, GATA6, LAMININ B1, and AFP as well as upregulation of trophectoderm-associated genes CDX2, GATA2, hCG-alpha, and hCG-beta. Immunostaining of preimplantation human embryos showed that NANOG was expressed in the inner cell mass of expanded blastocysts but not in earlier-stage embryos, consistent with a role in the maintenance of pluripotency. Taken together, our findings suggest that NANOG acts as a gatekeeper of pluripotency in human embryonic stem and carcinoma cells by preventing their differentiation to extraembryonic endoderm and trophectoderm lineages.