CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.
CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.
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DOI：
10.1042/bcj20160466
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发表时间：
2016-10-01
期刊：
影响因子：
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通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Zhou L;Yang K;Carpenter A;Lang RA;Andl T;Zhang Y
毛乳头(DP)中活跃的Wnt/β-catenin信号是出生后毛发周期所必需的。此外，在体外维持DP细胞的毛发诱导能力需要外加Wnt分子。然而，DP细胞是否是Wnt配体的重要来源，并诱导自分泌和旁分泌信号级联反应以促进成人毛囊的生长和再生仍然是未知的。为了解决这个问题，我们建立了一个动物模型，允许在CD133阳性(CD133+)DP细胞中诱导消融Wnless(Wls)，一种跨膜Wnt出口蛋白。CD133+细胞是DP中一种特殊的细胞亚群，具有诱导毛发的能力。在这里，我们表明，去除CD133+DP细胞中WLS的表达可以缩短出生后毛发的生长周期。突变毛囊不能进入完全生长期(毛发生长期)，并向快速退化方向发展。值得注意的是，当CD133+DP细胞失去WLS表达时，毛囊中DP的大小和生长期DP标记物VERSICAN的表达减少。进一步的分析表明，WLS缺陷的CD133+DP细胞导致基质角质形成细胞和黑素细胞的增殖和分化减少，而基质角质形成细胞和黑素细胞是毛囊结构和着色毛干形成所必需的。这些结果清楚地表明，CD133+DP细胞产生的Wnt配体通过维持DP细胞的诱导性和介导间充质与上皮间隔间的信号串扰，在出生后毛发生长中发挥重要作用。
Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment.