CONVERGENT GENESIS OF AN ADULT NEURAL CREST-LIKE DERMAL STEM CELL FROM DISTINCT DEVELOPMENTAL ORIGINS

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. In spite of 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.皮肤源性前体细胞（Skin-derived precursors，SKPs）是一类定居于毛囊龛中的多能真皮干细胞，与胚胎神经嵴前体细胞具有共通特性。本研究旨在探究SKPs及其内源性真皮前体细胞究竟起源于神经嵴，亦或是如真皮本身一般，具有多种发育起源。为此，我们采用了两种可用于谱系示踪的小鼠Cre重组酶系：靶向神经嵴来源细胞的Wnt1-cre，以及靶向体节来源细胞的Myf5-cre。通过将这些Cre重组酶系与报告基因小鼠杂交，我们证实：面部的内源性毛囊相关真皮前体细胞起源于神经嵴，背躯干中的此类前体细胞则起源于体节，其所产生的SKPs亦同此来源。尽管二者发育起源不同，这两个部位的SKPs功能却高度相似，即便在其分化为雪旺细胞的能力上亦是如此——而雪旺细胞此前被认为仅由神经嵴产生。通过基因微阵列开展的全局基因表达分析证实，面部SKPs与背侧SKPs具有极高的相似性，且与起源于侧板中胚层的腹侧真皮来源SKPs亦高度相近。然而，这些发育起源各异的SKPs，仍保留了少量可反映其各自发育起源的差异表达基因。综上，成人神经嵴样真皮前体细胞可由非神经嵴来源产生，这一发现对体内诸多神经内分泌细胞的研究具有广泛启示意义。