A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth
A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth
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DOI：
10.1016/j.stem.2019.01.011
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发表时间：
2019-04-04
期刊：
影响因子：
23.9
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
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作者：
Wang, Etienne C. E.;Dai, Zhenpeng;Christiano, Angela M.
通过局部应用 JAK 抑制剂可以诱导静止小鼠毛囊的毛发生长，这表明 JAK-STAT 信号传导对于维持毛囊干细胞 (HFSC) 处于静止状态是必需的。在这里，我们发现制瘤素 M (OSM)（一种 IL-6 家族细胞因子）通过 JAK-STAT5 发出信号以维持 HFSC 静止，从而负向调节毛发生长。 OSM 受体或 STAT5 的基因缺失可以诱导 HFSC 过早激活，这表明静息期是由毛囊生态位主动维持的。单细胞 RNA 测序表明，OSM 来源并非毛囊本身固有的，而是 TREM2(+) 巨噬细胞的子集，在静息毛囊中富集，并在 HFSC 激活前立即死亡。体内巨噬细胞功能的抑制足以诱导 HFSC 增殖和毛发周期诱导。这些结果共同阐明了 JAK-STAT 信号传导如何主动抑制毛发生长。
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.