Fibroblasts, both human and mouse, can be directly converted into neurons by adding the three transcription factors Ascl1, Brn2 and Myt1l. This suggests that cells can transdifferentiate without going through an embryonic phase. However, because fibroblast preparations contain some neural stem cells, among others, it isn't clear which cell type transdifferentiates. Marro et al. show definitively that terminally differentiated cells transdifferentiate. Using the same three transcription factors, they convert a homogeneous population of hepatocytes into cells with neuronal morphology and properties (Hep-iN cells). Hep-iN expression profiles resemble neuronal patterns more than hepatocyte patterns; of a set of genes with known function in liver, all of them were downregulated in Hep-iN cells, as were 85% of 149 genes preferentially expressed in liver. These results show that the same factors can downregulate both fibroblast-specific and hepatocyte-specific genes. Furthermore, the authors demonstrate that any cell type, even ones that derive from germ layers besides the ectodermal germ layer (which gives rise to neurons), can transdifferentiate into neurons. (Cell Stem Cell 9, 372–382, 2011)