Neural crest (NC) cells are multipotent stem cells that arise from the embryonic ectoderm, delaminate from the neural tube in early vertebrate development and migrate throughout the developing embryo, where they differentiate into various cell lineages. Here we show that multipotent and functional NC cells can be derived by induction with a growth factor cocktail containing FGF2 and IGF1 from cultures of human inter-follicular keratinocytes (KC) isolated from elderly donors. Adult NC cells exhibited longer doubling times as compared to neonatal NC cells, but showed limited signs of cellular senescence despite the advanced age of the donors and exhibited significantly younger epigenetic age as compared to KC. They also maintained their multipotency, as evidenced by their ability to differentiate into all NC-specific lineages including neurons, Schwann cells, melanocytes, and smooth muscle cells (SMC). Notably, upon implantation into chick embryos, adult NC cells behaved similar to their embryonic counterparts, migrated along stereotypical pathways and contributed to multiple NC derivatives in ovo . These results suggest that KC-derived NC cells may provide an easily accessible, autologous source of stem cells that can be used for treatment of neurodegenerative diseases or as a model system for studying disease pathophysiology and drug development.

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The origin of the neurons and glia in the olfactory system of vertebrates has been controversial, with different cell types attributed to being of ectodermal placode versus neural crest lineage, depending upon the species. Here, we use replication incompetent avian retroviruses to perform a prospective cell lineage analysis of either presumptive olfactory placode or neural crest cells during early development of the chick embryo. Surprisingly, the results reveal a dual contribution from both the olfactory placode and neural crest cells to sensory neurons in the nose and gonadotropin‐releasing hormone neurons migrating to the olfactory bulb. We also confirm that olfactory ensheathing glia cells are solely derived from the neural crest. Finally, our results show that neural crest cells and olfactory placode cells contribute to p63 positive cells, likely to be basal stem cells of the olfactory epithelium. Taken together, these finding provide evidence for previously unknown contributions of neural crest cells to some cell types in the chick olfactory system and help resolve previous discrepancies in the literature. Key Points Modified retroviruses were used to permanently label progenitor cells of the neural crest and olfactory placode for the long‐term lineage analysis of olfactory cells. Both neural crest cells and olfactory placode cells contribute to olfactory neurons and supporting cells of the olfactory epithelium. The gonadotropin‐releasing hormone neurons that arise in the nose and migrate toward the hypothalamus during development also receive contributions from both neural crest and placode cells.

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