CD49f(high) Defines a Distinct Skin Mesenchymal Stem Cell Population Capable of Hair Follicle Epithelial Cell Maintenance.
CD49f(high) Defines a Distinct Skin Mesenchymal Stem Cell Population Capable of Hair Follicle Epithelial Cell Maintenance.
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CD49f（高）定义了一种独特的皮肤间充质干细胞群，能够维持毛囊上皮细胞。
DOI：
10.1016/j.jid.2019.08.442
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发表时间：
2019
影响因子：
6.5
通讯作者：
Xiao Ran
中科院分区：
文献类型：
--
作者：
Yang Zhigang;Ma Shize;Cao Rui;Liu Ling;Cao Chunyan;Shen Zhihui;Fu Xin;Yan Li;Wang Qian;Liu Xia;Xiao Ran
真皮内有不同的间充质干细胞（MSC）群，它们在皮肤稳态和再生中扮演着与表皮干细胞同等重要的角色。然而，要可靠地鉴定和直接分离这些细胞的体内对应物仍然具有挑战性。利用表皮干细胞标记CD49f，我们在真皮中定义了一个cd491高分化的间充质亚群。体外和体内分化实验以及转录组分析表明，cd49fhighcell具有神经嵴样细胞特征。我们的研究结果表明，当毛囊上皮细胞与CD49fhighcells共培养时，可以诱导毛囊样出芽结构的形成和调控毛囊发育的关键基因的表达。我们还发现，CD49fhighcells激活了共培养毛囊上皮细胞中的Notch信号，而Notch信号的抑制导致表皮囊肿样球体和毛囊上皮细胞特性的丧失。此外，我们发现Itga7和CD49f是直接选择CD49fhighskin MSCs的有效生物标志物面板。我们的研究结果对皮肤中间充质干细胞的异质性和功能有了更深入的了解，并可能促进这些细胞的潜在翻译应用。
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 CD49fhighdistinct mesenchymal subpopulation in the dermis. In vitro and in vivo differentiation assays, and transcriptome analysis demonstrated that CD49fhighcells 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 CD49fhighcells. We also found that CD49fhighcells 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 CD49fhighskin 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.