Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Invest Dermatol. 2020 Mar;140(3):544-555.e9. doi: 10.1016/j.jid.2019.08.442. Epub 2019 Sep 6.
The dermis harbors distinct mesenchymal stem cell (MSC) populations, which play equally important roles as epidermal stem cells in skin homeostasis and regeneration. However, to reliably identify and directly isolate the in vivo counterpart of these cells is still challenging. Using the epidermal stem cell marker CD49f, we defined a CD49f distinct mesenchymal subpopulation in the dermis. In vitro and in vivo differentiation assays, and transcriptome analysis demonstrated that CD49f cells possess neural crest-like cell characteristics. Our results showed that the formation of hair follicle-like budding structure and the expressions of key genes regulating hair follicle development were induced when hair follicle epithelial cells were co-cultured with CD49f cells. We also found that CD49f cells activated Notch signaling in co-cultured hair follicle epithelial cells, whereas the inhibition of Notch signaling resulted in epidermal cyst-like spheres and loss of maintenance of hair follicle epithelial cell characteristics. Furthermore, we identified Itga7 and CD49f as an efficient biomarker panel for direct selection of CD49f skin MSCs. Our results lead to a deeper understanding of heterogeneity and the function of MSCs in the skin and may facilitate potential translational applications of these cells.
真皮中存在独特的间充质干细胞（MSC）群体，它们在皮肤稳态和再生中与表皮干细胞同样重要。然而，要可靠地识别和直接分离这些细胞的体内对应物仍然具有挑战性。我们使用表皮干细胞标志物 CD49f，在真皮中定义了一个 CD49f 独特的间充质亚群。体外和体内分化实验以及转录组分析表明，CD49f 细胞具有神经嵴样细胞特征。我们的结果表明，当毛囊上皮细胞与 CD49f 细胞共培养时，会诱导毛囊样芽状结构的形成和调节毛囊发育的关键基因的表达。我们还发现 CD49f 细胞在共培养的毛囊上皮细胞中激活了 Notch 信号通路，而 Notch 信号通路的抑制则导致表皮样囊肿样球体的形成，并丧失了维持毛囊上皮细胞特征的能力。此外，我们确定了 Itga7 和 CD49f 作为直接选择 CD49f 皮肤间充质干细胞的有效生物标志物组合。我们的研究结果加深了对皮肤中 MSC 异质性和功能的理解，并可能促进这些细胞的潜在转化应用。
