Induction of somatic cell reprogramming using the microRNA miR-302.
Since the discovery of pluripotent stem cells, scientists have envisioned their use in regenerative medicine. Unfortunately, such application of embryonic pluripotent stem cells has been impeded by ethical concerns as well as other obstacles. In light of this, the scientific community has begun to explore somatic cell reprogramming (SCR) as a means of producing induced pluripotent stem cells (iPSCs) from somatic cells. Although still far from being clinically applicable, SCR has become a hot research topic, with many groups working to understand its underlying mechanism. The standard method for inducing SCR is achieved by forced expression of four transcription factors defined by Yamanaka and Yu et al. Regrettably, iPSCs produced by the four-factor method tend to be tumorigenic, making them unsafe for clinical application. Recently, a new method has been identified to generate iPSCs through forced expression of an embryonic stem cell (ESC)-enriched microRNA, miR-302. This method holds a distinct advantage over the four-factor method because it can reprogram somatic cells to tumor-free iPSCs. Also, these miR-302-induced iPSCs, termed "mirPSCs," demonstrate a clear mechanism, which explains the process of reprogramming as a response to global DNA demethylation-the first sign of SCR. Nevertheless, miR-302-induced reprogramming is dose-dependent, and microRNA (miRNA) concentration must be within a specific range for the reprogramming to occur. In addition, excessive overexpression of miR-302 in mirPS cells must not occur; otherwise, they will undergo early senescence. mirPSCs represent a new source of pluripotent stem cells without the tumorigenicity traditionally attributed to iPSCs. Looking forward, the next challenge lies with surmounting senescence, an obstacle that often limits stem cell expansion and prevents researchers from growing the large quantities of iPSCs needed for therapeutic use.
Division of Regenerative Medicine, WJWU & LYNN Institute for Stem Cell Research, Santa Fe Springs, California, USA.
Karen
K
Kelley
Shi-Lung
SL
Lin
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D065150:Cellular Reprogramming / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs