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 suffi...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2011-11, Vol.29 (11), p.1752-1762
Main Authors: Zabierowski, Susan E., Baubet, Valerie, Himes, Benjamin, Li, Ling, Fukunaga‐kalabis, Mizuho, Patel, Sonal, McDaid, Ronan, Guerra, Matt, Gimotty, Phyllis, Dahamne, Nadia, Herlyn, Meenhard
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Line
Cell Movement - genetics
Cell Movement - physiology
Cellular Reprogramming - genetics
Cellular Reprogramming - physiology
Chick Embryo
Dedifferentiation
Humans
Melanocytes
Melanocytes - cytology
Melanocytes - metabolism
Neural Crest - cytology
Neural crest stem cells
Neural Stem Cells - cytology
Neural Stem Cells - metabolism
Notch
Receptor, Notch1 - genetics
Receptor, Notch1 - metabolism
Reprogramming
Stem Cells - cytology
Stem Cells - metabolism
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Summary: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
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.740