Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth.
Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth.
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DOI：
10.1371/journal.pone.0160425
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Zhou L;Xu M;Yang Y;Yang K;Wickett RR;Andl T;Millar SE;Zhang Y
毛囊毛乳头（DP）含有独特的CD 133+细胞亚群，已被证明具有毛囊诱导能力。通过测定内源性CD 133表达和使用CD 133-CreERT 2; ZsGreen 1报告小鼠进行谱系追踪，我们发现CD 133在小鼠毛发周期的生长期（生长初期）在DP细胞亚群中表达，但在生长初期不存在。然而，CD 133 + DP细胞如何与角质形成细胞相互作用以诱导毛发再生生长仍不清楚。Wnt/β-catenin一直被认为是毛囊形态发生、发育和再生所需的主要信号通路。在毛发生长阶段期间，在DP中观察到核Wnt/β-连环蛋白活性。在这里，我们表明，诱导表达的稳定形式的β-连环蛋白在CD 133 + DP细胞显着加速自发和脱毛诱导的毛发生长。然而，毛囊退化在这些突变体中不受影响。进一步分析表明，CD 133 + DP表达的β-连环蛋白增加上皮基质角质形成细胞的增殖和分化。CD 133 + DP细胞中Wnt/β-连环蛋白活性的上调也增加了每个生长期卵泡中增殖DP细胞的数量。我们的数据表明，β-连环蛋白信号增强了CD 133 + DP细胞促进出生后毛发生长的能力。
The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth.