title: Direct reprogramming of melanocytes to neural crest stem-like cells by one defined factor.
abstract: 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.
authors.affiliation: Cellular and Molecular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Zabierowski
authors.forename: Valerie
authors.initials: V
authors.lastname: Baubet
authors.forename: Benjamin
authors.initials: B
authors.lastname: Himes
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Mizuho
authors.initials: M
authors.lastname: Fukunaga-Kalabis
authors.forename: Sonal
authors.initials: S
authors.lastname: Patel
authors.forename: Ronan
authors.initials: R
authors.lastname: McDaid
authors.forename: Matt
authors.initials: M
authors.lastname: Guerra
authors.forename: Phyllis
authors.initials: P
authors.lastname: Gimotty
authors.forename: Nadia
authors.initials: N
authors.lastname: Dahmane
authors.forename: Nadia
authors.initials: N
authors.lastname: Dahamne
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology*; D002642:Chick Embryo; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D051881:Receptor, Notch1