Abstract
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.
Original language | English (US) |
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Pages (from-to) | 578-593.e19 |
Journal | Cell |
Volume | 182 |
Issue number | 3 |
DOIs | |
State | Published - Aug 6 2020 |
Keywords
- Adrb2
- hair follicle stem cells
- nerve-stem-cell interaction
- niche
- stem cell quiescence
- sympathetic nerve
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology