MicroRNAs in embryonic stem cells

Introduction Embryonic stem (ES) cells are cells which are isolated from the inner cell mass of embryos at the blastocyst stage of development (Evans and Kaufman, 1981; Martin, 1981; Brook and Gardner, 1997). These cells are characterized by their unique capabilities including self-renewal and the ability to maintain themselves as undifferentiated cells, as well as their pluripotent capacity to develop into any cell type. It is these two unique characteristics that make embryonic stem cells so interesting, as they present potential to be important scientific models as well as important therapeutic tools. Much research has been done toward understanding the delicate balance that ES cells possess, allowing them to maintain themselves as both undifferentiated and pluripotent. Though much still remains to be clarified, it is clear that many epigenetic elements such as DNA methylation, histone modifications, and microRNAs play crucial roles in this regulation (Boyer et al., 2005; Bernstein et al., 2006; Spivakov and Fisher, 2007; Benetti et al., 2008; Bibikova et al., 2008; Sinkkonen et al., 2008; Tiscornia and Izpisua Belmonte, 2010). MicroRNAs (miRNAs) are short sequences of RNA, 21–24 nucleotides (nt) in length, which play an integral role in the regulation of protein expression. MicroRNAs were first described with the discovery of lin-4 in Caenorhabditis elegans (Lee et al., 1993). However, the importance of this discovery was not fully appreciated until some years later, a decade ago, when what would be the second miRNA discovered, let-7, was described (Reinhart et al., 2000). Only then was it understood that the phenomenon was not an isolated occurrence, and that these short RNAs could actually play very important roles in gene regulation. Today it is known that there are more than 700 miRNAs in the human genome, and it has been predicted that likely over 60% of coding genes are targets of miRNAs. Bioinformatic predictions as well as experimental approaches indicate that one miRNA can have many, perhaps even hundreds of targets (He and Hannon, 2004; Friedman et al., 2009).