Direct reprogramming of melanocytes to neural crest stem-like cells by one defined factor.

Mouse and human somatic cells can either be reprogrammed to a pluripotent state or converted to another lineage with a combination of transcription factors suggesting that lineage commitment is a reversible process. Here we show that only one factor, the active intracellular form of Notch1, is sufficient to convert mature pigmented epidermal-derived melanocytes into functional multipotent neural crest stem-like cells. These induced neural crest stem cells (iNCSCs) proliferate as spheres under stem cell media conditions, re-express neural crest-related genes and differentiate into multiple neural crest derived mesenchymal and neuronal lineages. Moreover, iNCSCs are highly migratory and functional in ovo. These results demonstrate that mature melanocytes can be reprogrammed toward their primitive neural crest cell precursors through the activation of a single stem cell-related pathway. Reprogramming of melanocytes to iNCSCs may provide an alternate source of NCSCs for neuroregenerative applications.