Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state

• Published in: RNA (Cambridge) 2008-10, Vol.14 (10), p.2115-2124
• Main Authors: Lin, Shi-Lung, Chang, Donald C, Chang-Lin, Samantha, Lin, Chun-Hung, Wu, David T S, Chen, David T, Ying, Shao-Yao
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Cell Division - genetics; Cell Line, Tumor; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Embryonic Stem Cells - transplantation; Female; Gene Expression Profiling; Humans; Mice; Mice, SCID; MicroRNAs - genetics; MicroRNAs - physiology; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Pluripotent Stem Cells - transplantation; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Skin Neoplasms - therapy; Transfection; Transgenes
• ISSN: 1355-8382; 1469-9001
• DOI: 10.1261/rna.1162708

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 genome-wide 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.