title: Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state.
abstract: 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.
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. lins@usc.edu
authors.forename: Shi-Lung
authors.initials: SL
authors.lastname: Lin
authors.forename: Donald C
authors.initials: DC
authors.lastname: Chang
authors.forename: Samantha
authors.initials: S
authors.lastname: Chang-Lin
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: David T S
authors.initials: DT
authors.lastname: Wu
authors.forename: David T
authors.initials: DT
authors.lastname: Chen
authors.forename: Shao-Yao
authors.initials: SY
authors.lastname: Ying