Department of Dermatology, Columbia University, New York, NY, USA; National Skin Center, Singapore, Singapore.
Department of Dermatology, Columbia University, New York, NY, USA.
Cell Stem Cell. 2019 Apr 4;24(4):654-669.e6. doi: 10.1016/j.stem.2019.01.011. Epub 2019 Mar 28.
Hair growth can be induced from resting mouse hair follicles by topical application of JAK inhibitors, suggesting that JAK-STAT signaling is required for maintaining hair follicle stem cells (HFSCs) in a quiescent state. Here, we show that Oncostatin M (OSM), an IL-6 family cytokine, negatively regulates hair growth by signaling through JAK-STAT5 to maintain HFSC quiescence. Genetic deletion of the OSM receptor or STAT5 can induce premature HFSC activation, suggesting that the resting telogen stage is actively maintained by the hair follicle niche. Single-cell RNA sequencing revealed that the OSM source is not intrinsic to the hair follicle itself and is instead a subset of TREM2 macrophages that is enriched within the resting follicle and deceases immediately prior to HFSC activation. In vivo inhibition of macrophage function was sufficient to induce HFSC proliferation and hair cycle induction. Together these results clarify how JAK-STAT signaling actively inhibits hair growth.
毛发的生长可以通过局部应用 JAK 抑制剂从休眠的小鼠毛囊中诱导出来，这表明 JAK-STAT 信号通路对于维持毛囊干细胞（HFSCs）处于静止状态是必需的。在这里，我们发现，白细胞介素-6 家族细胞因子之一的 Oncostatin M（OSM）通过 JAK-STAT5 信号通路负调控毛发生长，从而维持 HFSC 的静止。OSM 受体或 STAT5 的基因缺失可诱导 HFSC 过早激活，这表明休止期毛囊的静止阶段是由毛囊微环境主动维持的。单细胞 RNA 测序显示，OSM 的来源并非毛囊本身所固有，而是在静止毛囊中富集的 TREM2 巨噬细胞的一个子集，并在 HFSC 激活前立即减少。体内抑制巨噬细胞功能足以诱导 HFSC 增殖和毛发生长周期诱导。这些结果共同阐明了 JAK-STAT 信号通路如何主动抑制毛发生长。
