Dysfunction of Hair Follicle Mesenchymal Progenitors Contributes to Age-Associated Hair Loss
Dysfunction of Hair Follicle Mesenchymal Progenitors Contributes to Age-Associated Hair Loss
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DOI：
10.1016/j.devcel.2020.03.019
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发表时间：
2020-04-20
影响因子：
11.8
通讯作者：
Biernaskie, Jeff
中科院分区：
文献类型：
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作者：
Shin, Wisoo;Rosin, Nicole L.;Biernaskie, Jeff
由于毛囊（HF）上皮祖细胞及其间充质生态位的损伤，皮肤老化伴随着脱发。这种诱导间质，称为真皮乳头（DP），经历进行性细胞丢失和最终的小型化，有助于HF的发病。通过激光消融和命运定位，我们发现HF真皮干细胞（hfDSC）重建受损的DP并维持毛发生长，表明hfDSC功能障碍可能引发诱导生态位的退化。24个月的命运图谱显示hfDSC逐渐耗尽，衰老的hfDSC体内克隆分析显示自我更新和偏分化受损。单细胞RNA-seq证实hfdsc是中心前体，引起不同的间充质轨迹。在衰老皮肤中，hfdsc表现出衰老样特征，衰老相关的分泌表型在衰老的HF间质中被鉴定出来。这些结果阐明了HF内的成纤维细胞动力学，并表明间充质祖细胞池的进行性功能障碍导致了与年龄相关的脱发。
Skin aging is accompanied by hair loss due to impairments in hair follicle (HF) epithelial progenitor cells and their mesenchymal niche. This inductive mesenchyme, called dermal papilla (DP), undergoes progressive cell loss and eventual miniaturization that contributes to HF pathogenesis. Using laser ablation and fate mapping, we show that HF dermal stem cells (hfDSCs) reconstitute the damaged DP and maintain hair growth, suggesting that hfDSC dysfunction may trigger degeneration of the inductive niche. Fate mapping over 24 months revealed progressive hfDSC depletion, and in vivo clonal analysis of aged hfDSCs showed impaired self-renewal and biased differentiation. Single-cell RNA-seq confirmed hfDSCs as a central precursor, giving rise to divergent mesenchymal trajectories. In aged skin, hfDSCs exhibited senescent-like characteristics, and senescence-associated secretory phenotypes were identified in the aging HF mesenchyme. These results clarify fibroblast dynamics within the HF and suggest that progressive dysfunction within the mesenchymal progenitor pool contributes to age-related hair loss.