The expanding horizon of MicroRNAs in cellular reprogramming

Research over the last few years in cellular reprogramming has enlightened the magical potential of microRNAs (miRNAs) in changing the cell fate from somatic to pluripotent. Recent investigations on exploring the role(s) of miRNAs in somatic cell reprogramming revealed that they target a wide range of molecules and refine their protein output. This leads to fine tuning of distinct cellular processes including cell cycle, signalling pathways, transcriptional activation/silencing and epigenetic modelling. The concerted actions of miRNA on different pathways simultaneously strengthen the transition from a differentiated to de-differentiated state. Despite the well characterized transcriptional and epigenetic machinery underlying somatic cell reprogramming, the molecular circuitry for miRNA mediated cellular reprogramming is rather fragmented. This review summarizes recent findings addressing the role of miRNAs in inducing or suppressing reprogramming thus uncovering novel potentials of miRNAs as regulators of induced pluripotency maintenance, establishment and associated signalling pathways. Our bioinformatic analysis sheds light on various unexplored biological processes and pathways associated with reprogramming inducing miRNAs, thus helps in identifying roadblocks to full reprogramming. Specifically, the biological significance of highly conserved and most studied miRNA cluster, i.e. miR-302-367, in reprogramming is also highlighted. Further, roles of miRNAs in the differentiation of neurons from iPSCs are discussed. A recent approach of direct conversion or transdifferentiation of differentiated cells into neurons by miRNAs is also elaborated. This approach is now widely gaining impetus for the generation of neurological patient's brain cells directly from his/her somatic cells in an efficient and safe manner. Thus, decoding the intricate circuitry between miRNAs and other gene regulatory networks will not only uncover novel pathways in the direct reprogramming of somatic cells but will also open new avenues in stem cell biology.