MicroRNA Regulation Along the Course of Cellular Reprogramming to Pluripotency

Generation of patient-specific stem cells has been a long-held aim of many developmental biologists. Apart from providing a source for stem cell therapies, these cells have the potential to be utilized in a number of scenarios like disease modeling, drug screening and studying normal development. Various approaches have been used to reprogram terminally differentiated cells to a pluripotent state with varying efficiencies and limitations. The nuclear transfer had been the most successful method for reprogramming until recently. Shinya Yamanaka in 2006 published a seminal study wherein, by using a cocktail of stem cell transcription factors famously called Yamanaka factors, the differentiated cells were reprogrammed to a pluripotent state. These cells, called induced pluripotent stem (iPS) cells, were later generated by various laboratories using a different combination of molecules. Importantly, induced pluripotency is a state that is achieved in a stepwise manner with landmark steps. Various molecules including microRNAs (miRNAs) are activated or repressed at these steps to ensure a successful transition to pluripotency. The precise regulation of miRNAs is important as they collectively regulate myriads of mRNAs representing specific pathways important for steering cellular fate towards stemness. Owing to their significance, miRNAs have been constituents of cocktails used for iPSCs generation. This review aims at discussing the stepwise regulation of miRNAs and their significance along the path to reprogramming.