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

Abstract

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.

Regulation of skin aging and heart development by TAp63

“…TAp63 is expressed by SKPs, which either derive from somites or originate from the neural crest cells. 41 Contrary to what had been observed with hair follicles SKPs, downregulation of TAp63 did not influence the proliferation capacity and differentiation potential of human bone marrow-derived mesenchymal stem cells while protecting them against apoptosis. 52 This observation suggests two distinct roles for TAp63 in mesenchymal stem cells versus neural crest-derived stem cells, opening doors for further investigations.…”

“…Lineage tracing analysis allowed the authors to conclude that SKPs, and the endogenous dermal precursors from which they derive, originate from the neural crest in the face and the somites in the dorsal trunk, but despite these different origins, they both generate precursors with a highly similar phenotype. 41 …”

Hair Follicle Reconstruction and Stem Cells

“…In spite of diferent embryological origin of DPs from diferent sites of the body, their functional properties are quite similar. Analysis of global gene expression using microarrays demonstrated a very high degree of similarity between facial and trunk dermal hair-associated cells indicating phenotypic convergence within HF niche [38]. DP cells have been quite profoundly investigated but their isolation and long-term cultivation is not a trivial task yet.…”

Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

“…hSKP are a multipotent cell population isolated from human dermal (fore)skin [27][28][29]. These neural crest related ASC can also be isolated from skin of the abdomen [30], breast [30], arm [31], face [32], and scalp [33] mostly upon aesthetic interventions.…”