Journal
STEM CELLS
Volume 29, Issue 11, Pages 1752-1762Publisher
WILEY
DOI: 10.1002/stem.740
Keywords
Notch; Melanocytes; Neural crest stem cells; Reprogramming; Dedifferentiation
Categories
Funding
- NIH [CA 076674, CA 025874, CA 093,372]
- [5 T32 CA09171]
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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 (NC) stem-like cells. These induced NC stem cells (iNCSCs) proliferate as spheres under stem cell media conditions, re-express NC-related genes, and differentiate into multiple NC-derived mesenchymal and neuronal lineages. Moreover, iNCSCs are highly migratory and functional in vivo. These results demonstrate that mature melanocytes can be reprogrammed toward their primitive NC 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. STEM CELLS 2011;29:1752-1762
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