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Functional neurons and melanocytes induced from immortal lines of postnatal neural crest-like stem cells

Elena V. Sviderskaya^*,1, David J. Easty^*,2, Mark A. Lawrence^*, Daniel P. Sánchez^,3, Yuri A. Negulyaev, Ricken H. Patel^*, Praveen Anand, Yuri E. Korchev and Dorothy C. Bennett^*

^* Centre for Molecular and Metabolic Signalling, Division of Basic Medical Sciences, St. George’s, University of London, London, UK;

London Centre for Nanotechnology, Division of Medicine, Imperial College, London, UK;

Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia; and

Imperial College Faculty of Medicine, Peripheral Neuropathy Unit, Hammersmith Hospital Campus, London, UK

¹ Correspondence: St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK. E-mail: esviders{at}sgul.ac.uk

Stem cells, that is, cells that can both reproduce themselves and differentiate into functional cell types, attract much interest as potential aids to healing and disease therapy. Embryonic neural crest is pluripotent and generates the peripheral nervous system, melanocytes, and some connective tissues. Neural-crest-related stem cells have been reported previously in postnatal skin: committed melanocytic stem cells in the hair follicle, and pluripotent cell types from the hair follicle and papilla that can produce various sets of lineages. Here we describe novel pluripotent neural crest-like stem cells from neonatal mouse epidermis, with different potencies, isolated as 3 independent immortal lines. Using alternative regulatory factors, they could be converted to large numbers of either Schwann precursor cells, pigmented melanocytes, chondrocytes, or functional sensory neurons showing voltage-gated sodium channels. Some of the neurons displayed abundant active TRPV1 and TRPA1 receptors. Such functional neurons have previously been obtained in culture only with difficulty, by explantation. The system was also used to generate comparative gene expression data for the stem cells, melanocytes, and melanoblasts that sufficiently explain the lack of pigment in melanoblasts and provide a rationale for some genes expressed apparently ectopically in melanomas, such as ephrin receptors.—Sviderskaya, E. V., Easty, D. J., Lawrence, M. A., Sánchez, D. P., Negulyaev, Y. A., Patel, R. H., Anand, P., Korchev, Y. E., Bennett, D. C. Functional neurons and melanocytes induced from immortal lines of postnatal neural crest-like stem cells.

Key Words: determination • differentiation • melanoma • chondrocyte • Schwann cell