Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state
Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state
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DOI：
10.1261/rna.1162708
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发表时间：
2008-10-01
期刊：
影响因子：
4.5
通讯作者：
Ying, Shao-Yao
中科院分区：
文献类型：
--
作者：
Lin, Shi-Lung;Chang, Donald C.;Ying, Shao-Yao
干细胞的更新在自我控制的细胞分裂方面不同于癌细胞的生长。Mir-302microRNA(MiRNA)家族(mir-302s)在生长缓慢的人胚胎干细胞中表达最丰富，在细胞分化和增殖后迅速减少。因此，在本研究中，mir-302s被视为维持ES细胞更新和多能性的关键因子之一。使用基于Pol-II的内含子miRNA表达系统将mir-302s转基因导入多个人癌细胞系。Mir-302转基因细胞，即miRNA诱导的多能干细胞，不仅表达许多关键的ES细胞标志，如Oct3/4、SSEA-3、SSEA-4、Sox2和Nanog，而且具有高度去甲基化的基因组，类似于重编程的合子基因组。微阵列分析进一步表明，MirPS与人ES-H1和H9细胞之间的全基因组基因表达模式有超过86%的相似性。在体外的分子引导下，这些MirPS细胞可以分化为不同的组织细胞类型，如神经元、软骨细胞、成纤维细胞和精原细胞样原始细胞。基于这些发现，我们得出结论，mir-302不仅具有将癌细胞重新编程为ES样多能性状态的功能，而且还可以在无饲养层培养条件下维持这种状态，这可能为治疗干预提供很好的机会。
Renewal of stem cells differs from cancer cell growth in self-controlled cell division. The mir-302 microRNA (miRNA) family (mir-302s) is expressed most abundantly in slow-growing human embryonic stem (ES) cells, and quickly decreases after cell differentiation and proliferation. Therefore, mir-302s was investigated as one of the key factors essential for maintenance of ES cell renewal and pluripotency in this study. The Pol-II-based intronic miRNA expression system was used to transgenically transfect the mir-302s into several human cancer cell lines. The mir-302-transfected cells, namely, miRNA-induced pluripotent stem (mirPS) cells, not only expressed many key ES cell markers, such as Oct3/4, SSEA-3, SSEA-4, Sox2, and Nanog, but also had a highly demethylated genome similar to a reprogrammed zygotic genome. Microarray analyses further revealed that genomewide gene expression patterns between the mirPS and human ES H1 and H9 cells shared over 86% similarity. Using molecular guidance in vitro, these mirPS cells could differentiate into distinct tissue cell types, such as neuron-, chondrocyte-, fibroblast-, and spermatogonia- like primordial cells. Based on these findings, we conclude that mir-302s not only function to reprogram cancer cells into an ES-like pluripotent state but also to maintain this state under a feeder-free cultural condition, which may offer a great opportunity for therapeutic intervention.