Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study interactions across epithelium, mesenchyme, and nerves. Here, we show that APMs and sympathetic nerves form a dual-component niche to modulate hair follicle stem cell (HFSC) activity. Sympathetic nerves form synapse-like structures with HFSCs and regulate HFSCs through norepinephrine, whereas APMs maintain sympathetic innervation to HFSCs. Without norepinephrine signaling, HFSCs enter deep quiescence by down-regulating the cell cycle and metabolism while up-regulating quiescence regulators Foxp1 and Fgf18. During development, HFSC progeny secretes Sonic Hedgehog (SHH) to direct the formation of this APM-sympathetic nerve niche, which in turn controls hair follicle regeneration in adults. Our results reveal a reciprocal interdependence between a regenerative tissue and its niche at different stages and demonstrate sympathetic nerves can modulate stem cells through synapse-like connections and neurotransmitters to couple tissue production with demands.

立毛（鸡皮疙瘩）需要毛囊、竖毛肌 (APM) 和交感神经的协同作用，为研究上皮、间充质和神经之间的相互作用提供了一个模型。在这里，我们显示 APM 和交感神经形成双组分生态位来调节毛囊干细胞 (HFSC) 活动。交感神经与 HFSCs 形成突触样结构，并通过去甲肾上腺素调节 HFSCs，而 APMs 维持对 HFSCs 的交感神经支配。在没有去甲肾上腺素信号的情况下，HFSCs 通过下调细胞周期和代谢同时上调静止调节因子Foxp1和Fgf18进入深度静止. 在发育过程中，HFSC 后代会分泌 Sonic Hedgehog (SHH) 来指导这种 APM 交感神经生态位的形成，进而控制成人毛囊的再生。我们的结果揭示了再生组织与其不同阶段的生态位之间的相互依赖，并证明交感神经可以通过突触样连接和神经递质调节干细胞，以将组织生产与需求相结合。