A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth.,Cell Stem Cell

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A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-03-28 , DOI: 10.1016/j.stem.2019.01.011
Etienne C E Wang ₁ , Zhenpeng Dai ₂ , Anthony W Ferrante ₃ , Charles G Drake ₄ , Angela M Christiano ₅

Affiliation

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.

中文翻译：

TREM2+ 真皮巨噬细胞的一个子集分泌制瘤素 M 以维持毛囊干细胞静止并抑制毛发生长。

通过局部应用 JAK 抑制剂，可以从静止的小鼠毛囊诱导毛发生长，这表明 JAK-STAT 信号是维持毛囊干细胞 (HFSC) 处于静止状态所必需的。在这里，我们表明制瘤素 M (OSM) 是一种 IL-6 家族细胞因子，它通过 JAK-STAT5 发出信号来负向调节毛发生长，以维持 HFSC 静止。OSM 受体或 STAT5 的基因缺失可诱导 HFSC 过早激活，表明静息休止期由毛囊生态位主动维持。单细胞 RNA 测序表明，OSM 来源并不是毛囊本身固有的，而是 TREM2+ 巨噬细胞的一个子集，它在静息毛囊内富集，并在 HFSC 激活前立即死亡。巨噬细胞功能的体内抑制足以诱导 HFSC 增殖和毛发周期诱导。这些结果共同阐明了 JAK-STAT 信号如何积极抑制毛发生长。

更新日期：2019-03-29

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