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

Yulia Shwartz, Meryem Gonzalez-Celeiro, Chih Lung Chen, 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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Pages (from-to)578-593.e19
Issue number3
StatePublished - Aug 6 2020


  • 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


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