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Generation of CNS cell types from PNS stem cells

      The neural crest gives rise to the neurons and glial cells of the peripheral nervous system (PNS). Self-renewing neural crest-derived stem cells (NCSCs) are present in migratory neural crest and various postmigratory locations, including peripheral ganglia. We previously demonstrated that NCSCs from embryonic mouse dorsal root ganglia (DRG) are reprogrammed in neurosphere (NS) cultures in the presence of EGF and FGF. rNCSCs generate exclusively central nervous system (CNS) progeny, both in vitro and upon transplantation into the mouse brain (Binder et al., (2011) J. Neurosci. 31, 6379-91). Here we address the timing and mechanisms underlying the reprogramming. Most of the cells acquire CNS characteristics at passage 2, reaching a stable proportion of >90% of Olig2+ cells at passage 3, which is maintained up to at least passage 10. The PNS marker p75 is completely lacking from passage 3 onwards. Under differentiation conditions 3rd passage NS cells generate Olig2+/O4+ oligodendrocytes, GFAP + cells with astrocyte morphology and CNS neurons.
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