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

doi:10.1016/j.cell.2020.06.031

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

Cell. 2020 Aug 6;182(3):578-593.e19. doi: 10.1016/j.cell.2020.06.031. Epub 2020 Jul 16.

Authors

Affiliations

¹ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
² Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
³ Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan.
⁴ Electron Microscopy Resource Center, The Rockefeller University, New York, NY 10065, USA.
⁵ Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
⁶ Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
⁷ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
⁸ Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
⁹ Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan; Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 100, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan. Electronic address: drsjlin@ntu.edu.tw.
¹⁰ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: yachieh_hsu@harvard.edu.

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.

Keywords: Adrb2; hair follicle stem cells; nerve-stem-cell interaction; niche; stem cell quiescence; sympathetic nerve.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Accessory Nerve / cytology
Accessory Nerve / physiology*
Animals
Cell Cycle / genetics
Cold Temperature
Female
Fibroblast Growth Factors / metabolism
Forkhead Transcription Factors / metabolism
Gene Expression Profiling
Hair / cytology
Hair / growth & development*
Hair / physiology
Hair Follicle / cytology*
Hair Follicle / growth & development
Hair Follicle / metabolism
Hedgehog Proteins / metabolism*
Humans
Male
Mice
Mice, Inbred C57BL
Norepinephrine / metabolism*
Piloerection
RNA-Seq
Receptors, Adrenergic, beta-2 / deficiency
Receptors, Adrenergic, beta-2 / genetics
Receptors, Adrenergic, beta-2 / metabolism
Repressor Proteins / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics*
Smoothened Receptor / genetics
Smoothened Receptor / metabolism
Stem Cell Niche
Stem Cells / cytology
Stem Cells / metabolism*
Stem Cells / physiology*
Sympathetic Nervous System / cytology
Sympathetic Nervous System / physiology
Synapses / physiology

Substances

ADRB2 protein, mouse
Forkhead Transcription Factors
Foxp1 protein, mouse
Hedgehog Proteins
Receptors, Adrenergic, beta-2
Repressor Proteins
Smo protein, mouse
Smoothened Receptor
fibroblast growth factor 18
Fibroblast Growth Factors
Norepinephrine

Abstract

Publication types

MeSH terms

Substances

Grants and funding