signatures were robustly silenced in both fibroblast- and hepatocyte-derived iN cells. This led us to the remarkable conclusion that the exact same three transcription factors can not only induce a neuronal program but can also downregulate two unrelated donor transcriptional programs. Detailed gene expression analysis on the population and single cell level indicated that iN cells possess a small degree of epigenetic memory of their donor cells, but these transcriptional remnants decreased over time. It will be interesting to investigate the molecular mechanism underlying the transcriptional silencing that occurs, and to see whether it is similar to mechanisms that are used during cell fate specification in the embryo. Given the substantial differences between the fibroblast and liver transcriptional programs, it seems unlikely that the transcriptional silencing is directly mediated by the neuronal transcription factors themselves. Nevertheless, it is a formal possibility that the BAM factors target and inhibit a large number of key lineage-determining factors representing many non-neuronal cell fates. Alternatively, the mutual lineage switch could be caused by a more general mechanism. Perhaps when cells are becoming specified to one particular lineage a process becomes activated that leads to transcriptional silencing of many other lineage programs. For example, lineage-determining
