Open AccessDirect Reprogramming of Melanocytes to Neural Crest Stem‐Like Cells by One Defined Factor
Author(s) -
Zabierowski Susan E.,
Baubet Valerie,
Himes Benjamin,
Li Ling,
Fukunagakalabis Mizuho,
Patel Sonal,
McDaid Ronan,
Guerra Matt,
Gimotty Phyllis,
Dahamne Nadia,
Herlyn Meenhard
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.740
Subject(s) - biology , reprogramming , neural crest , microbiology and biotechnology , stem cell , induced pluripotent stem cell , multipotent stem cell , mesenchymal stem cell , neural stem cell , cellular differentiation , induced stem cells , adult stem cell , cell , genetics , progenitor cell , embryonic stem cell , gene , embryo
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. S TEM C ELLS 2011;29:1752–1762