Tumour Suppression Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Genomics Core Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Oncogene. 2014 May 8;33(19):2513-9. doi: 10.1038/onc.2013.196. Epub 2013 Jun 10.
NANOG is a key transcription factor for pluripotency in embryonic stem cells. The analysis of NANOG in human cells is confounded by the presence of multiple and highly similar paralogs. In particular, there are three paralogs encoding full-length proteins, namely, NANOG1, NANOG2 and NANOGP8, and at least eight additional paralogs that do not encode full-length NANOG proteins. Here, we have examined NANOG family expression in human embryonic stem cells (hESCs) and in human cancer cell lines using a multi-NANOG PCR that amplifies the three functional paralogs and most of the non-functional ones. As anticipated, we found that hESCs express large amounts of NANOG1 and, interestingly, they also express NANOG2. In contrast, most human cancer cells tested express NANOGP8 and the non-coding paralogs NANOGP4 and NANOGP5. Notably, in some cancer cell lines, the NANOG protein levels produced by NANOGP8 are comparable to those produced by NANOG1 in pluripotent cells. Finally, we show that NANOGP8 is as active as NANOG1 in the reprogramming of human and murine fibroblasts into induced pluripotent stem cells. These results show that cancer-associated NANOGP8 can contribute to promote de-differentiation and/or cellular plasticity.
NANOG 是胚胎干细胞多能性的关键转录因子。由于存在多个高度相似的同源基因，人类细胞中 NANOG 的分析变得复杂。特别是，有三个编码全长蛋白的同源基因，即 NANOG1、NANOG2 和 NANOGP8，以及至少八个不编码全长 NANOG 蛋白的其他同源基因。在这里，我们使用一种可以扩增三个功能性同源基因和大多数非功能性同源基因的多 NANOG PCR，检测了人类胚胎干细胞（hESC）和人类癌细胞系中的 NANOG 家族表达情况。正如预期的那样，我们发现 hESC 大量表达 NANOG1，而且有趣的是，它们也表达 NANOG2。相比之下，大多数测试的人类癌细胞表达 NANOGP8 以及非编码同源基因 NANOGP4 和 NANOGP5。值得注意的是，在一些癌细胞系中，NANOGP8 产生的 NANOG 蛋白水平与多能细胞中 NANOG1 产生的 NANOG 蛋白水平相当。最后，我们表明 NANOGP8 与 NANOG1 一样能够有效地将人类和鼠源成纤维细胞重编程为诱导多能干细胞。这些结果表明，与癌症相关的 NANOGP8 可以促进去分化和/或细胞可塑性。
