Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Canada.
Stem Cells. 2010 Nov;28(11):2027-40. doi: 10.1002/stem.525.
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.
皮肤衍生前体细胞 (SKP) 是多能真皮干细胞,存在于毛囊龛中,与胚胎神经嵴前体细胞具有共同特性。在这里,我们想知道 SKP 及其内源性真皮前体细胞是否起源于神经嵴,或者是否像真皮本身一样起源于多种发育来源。为此,我们使用了两种不同的小鼠 Cre 线,允许我们进行谱系追踪:Wnt1-cre,它靶向来自神经嵴的细胞,以及 Myf5-cre,它靶向体节起源的细胞。通过将这些 Cre 线与报告小鼠杂交,我们表明面部的内源性毛囊相关真皮前体细胞来自神经嵴,而背部主干的则来自体节,它们产生的 SKP 也是如此。尽管这些 SKP 具有不同的发育起源,但来自这两个位置的 SKP 在功能上是相似的,甚至在分化为施万细胞的能力方面也是如此,而施万细胞仅被认为是由神经嵴产生的。使用微阵列进行的全基因表达分析证实,面部和背部 SKP 表现出非常高的相似性,并且它们也与来自腹侧真皮的 SKP 非常相似,腹侧真皮具有侧板起源。然而,这些发育上不同的 SKP 也保留了少数基因的差异表达,这些基因反映了它们的发育起源。因此,来自非神经嵴起源的成年神经嵴样真皮前体细胞可以被产生,这一发现对体内许多神经内分泌细胞具有广泛的意义。