Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells.

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. • The hair follicle instructs the formation of the APM-sympathetic nerve unit via SHH • APM maintains sympathetic innervation to HFSCs • Sympathetic nerve activates HFSCs via synapse-like contacts and norepinephrine • Cold stimulates not only goosebumps but also hair growth The arrector pili muscle and the sympathetic neuron form a dual-component niche that regulates hair follicle stem cells—the sympathetic neuron regulates stem cells directly with norepinephrine via synapse-like structures, whereas the arrector pili muscle maintains sympathetic innervation to stem cells. Through these three connected cell types, cold stimulates not only goosebumps but also stem cell activation. [ABSTRACT FROM AUTHOR]