The fact that the vast majority of reprogramming factors known to date are transcriptional regulators is not surprising given their ability to efficiently activate gene expression, and it also fits with the idea that there are “master regulators” and “terminal selectors” for specific lineages (Weintraub et al., 1989, Hobert, 2011). It is surprising, however, that miRNAs, which are thought to function predominantly through downregulation of gene activity, seem to be very powerful agents to mediate reprogramming. Two independent groups have recently derived human and mouse iPS cells by adding miRNAs, in the absence of any additional transcription factors (Anokye-Danso et al., 2011; Miyoshi et al., 2011). Similarly, Yoo et al. 2011 showed that by introducing miR-9/9* and miR-124, human fibroblasts can be reprogrammed into cells with neuron-like morphologies expressing the pan-neuronal marker MAP2. While these phenotypic changes are truly remarkable, the miRNAs alone were not sufficient to induce functional iN cells. However, the addition of the transcription factors NEUROD2, ASCL1, and MYT1L greatly increased the conversion efficiencies and led to the formation of iN cells from fetal and adult human
