MicroRNAs in pluripotency, reprogramming and cell fate induction

Pluripotent stem cells display a unique expression pattern of microRNAs (miRNAs). These ~ 22 nucleotide non-coding RNAs have established a crucial role in controlling gene expression of pluripotent stem cells at the post-transcriptional level. Recent studies made important advances in identifying miRNA regulated processes like de novo DNA methylation, progression of the cell cycle and regulation of cell fate decision. miRNAs have also the ability to reprogram somatic cells to pluripotent stem cells and on the other hand, to induce differentiation of pluripotent stem cells into distinct somatic lineages. Previously it was published that miRNAs can direct reprogramming on its own. Here we provide evidence and critically discuss that the effect of miRNA depends on co-expression of the classical reprogramming factors. During transition between these different cell fates distinct miRNAs adjust the levels of specific transcriptional programs and confer robustness to differentiation processes. This results in a complex network between miRNAs and their targets. The fact that miRNAs itself can also be regulated by its targets establishes complex regulatory loops. Based on bioinformatical predictions, each miRNA theoretically has hundreds of target genes making it even more challenging to understand the complete network between miRNAs and their targets.