Gene silencing in human embryonic stem cells by RNA interference

RNA interference (RNAi) is a post-transcriptional conserved mechanism, which is present in a wide range of organisms and leads to specific gene silencing. The effector molecules in this process are double-stranded RNAs (dsRNAs) that are homologous in sequence to the silenced gene and are processed into small interfering RNAs (siRNAs) by an enzyme called Dicer. Consequently, siRNAs are incorporated into an RNA-induced silencing complex, which finds and cleaves the target mRNA. Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool for gene silencing in living organisms. Human embryonic stem cells (HESCs) have the ability to both self-renew and differentiate into cell types of all three germ layers. HESCs open new avenues for understanding some of the very early lineage determination events that occur during embryogenesis and are also considered as an important source of cells for cell replacement therapies. Understanding how the signaling pathways orchestrate and direct HESC differentiation toward certain cell types is critical for basic research. In this way RNAi appears to be a valuable tool in stem cell biology for dissecting the pathways involved in differentiation, lineage segregation and production of cells for cell therapy. Here, we review the prospects of combining RNAi and HESC manipulation for both basic research and future therapies.