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Skin‐derived precursors (SKPs) are multipotent dermal stem cells that reside within a hair follicle niche and that share properties with embryonic neural crest precursors. Here, we have asked whether SKPs and their endogenous dermal precursors originate from the neural crest or whether, like the dermis itself, they originate from multiple developmental origins. To do this, we used two different mouse Cre lines that allow us to perform lineage tracing:  Wnt1‐cre , which targets cells deriving from the neural crest, and  Myf5‐cre , which targets cells of a somite origin. By crossing these Cre lines to reporter mice, we show that the endogenous follicle‐associated dermal precursors in the face derive from the neural crest, and those in the dorsal trunk derive from the somites, as do the SKPs they generate. Despite these different developmental origins, SKPs from these two locations are functionally similar, even with regard to their ability to differentiate into Schwann cells, a cell type only thought to be generated from the neural crest. Analysis of global gene expression using microarrays confirmed that facial and dorsal SKPs exhibit a very high degree of similarity, and that they are also very similar to SKPs derived from ventral dermis, which has a lateral plate origin. However, these developmentally distinct SKPs also retain differential expression of a small number of genes that reflect their developmental origins. Thus, an adult neural crest‐like dermal precursor can be generated from a non‐neural crest origin, a finding with broad implications for the many neuroendocrine cells in the body. STEM CELLS 2010;28:2027–2040

Convergent Genesis of an Adult Neural Crest‐Like Dermal Stem Cell from Distinct Developmental Origins