Yulia Shwartz, Meryem Gonzalez-Celeiro, Chih-Lung, H. Amalia Pasolli, Shu-Hsien Sheu, Sabrina Mai-Yi Fan, Farnaz Shamsi, Steven Assaad, Edrick Tai-Yu Lin, Bing Zhang, Pai-Chi Tsai, Megan He, Yu-Hua Tseng, Sung-Jan Lin, Ya-Chieh Hsu.

Cell, Volume 182, Issue 3, Pages 578-593.e19 (2020)

https://www.sciencedirect.com/science/article/pii/S0092867420308084

Summary

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.