Cited by 97Hair Growth and DisordersSkin and Cellular Biology ResearchHearing, Cochlea, Tinnitus, Genetics

Hair shaft miniaturization causes stem cell depletion through mechanosensory signals mediated by a Piezo1-calcium-TNF-α axis

Open access
Xie, Yuhua, Chen, Daoming, Jiang, Kaiju, Song, Lifang, Qian, Nannan, Du, Yingxue, Yang, Yong, Wang, Fengchao +1 more·2022·Cell Stem Cell

Abstract

In aging, androgenic alopecia, and genetic hypotrichosis disorders, hair shaft miniaturization is often associated with hair follicle stem cell (HFSC) loss. However, the mechanism causing this stem cell depletion in vivo remains elusive. Here we show that hair shaft loss or a reduction in diameter shrinks the physical niche size, which results in mechanical compression of HFSCs and their apoptotic loss. Mechanistically, cell compression activates the mechanosensitive channel Piezo1, which triggers calcium influx. This confers tumor necrosis factor alpha (TNF-α) sensitivity in a hair-cycle-dependent manner in otherwise resistant HFSCs and induces ectopic apoptosis. Persistent hair shaft miniaturization during aging and genetic hypotrichosis disorders causes long-term HFSC loss by inducing continuous ectopic apoptosis through Piezo1. Our results identify an unconventional role of the inert hair shaft structure as a functional niche component governing HFSC survival and reveal a mechanosensory axis that regulates physical-niche-atrophy-induced stem cell depletion in vivo.

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Registry

Crossref · 10.1016/j.stem.2021.09.009

Cites

64 of 64 references verified0 citation errors · 0 not checkable

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  • Mechanical sensitivity of pressure receptors in mouse hair follicle stem cells depends on Piezo1.

    “Mechanical sensitivity of pressure receptors in mouse hair follicle stem cells depends on Piezo1.69”
  • The ageing skin is characterized by niche stiffening and hair shaft miniaturization, which are accompanied by defects in hair follicle stem cells (HFSCs).

    “The ageing skin is characterized by niche stiffening and hair shaft miniaturization, which are accompanied by defects in hair follicle stem cells (HFSCs)83,84.”
  • In the skin, niche stiffening and persistent hair shaft miniaturization during ageing can contribute to HFSC ageing via a reduction in promoter bivalency in HFSCs and via a PIEZO1-TNF mechanism.

    “In the skin, niche stiffening and persistent hair shaft miniaturization during ageing can also contribute to HFSC ageing via a reduction in promoter bivalency in HFSCs84 and via a PIEZO1–TNF mechanism83.”

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Authors
Xie, Y., Chen, D., Jiang, K., Song, L., Qian, N., Du, Y., Yang, Y., Wang, F., & Chen, T.
Affiliations
  • National Institute of Biological Sciences, Beijing (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Chen, Ting
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2022-01
Volume
29
Issue
1
Pages
70-85.e6
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W3203743280
Cited by
97
References
64
Citations by year
2026: 23 · 2025: 26 · 2024: 18 · 2023: 15 · 2022: 14 · 2021: 1
FWCI
13.74
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (32070873)
  • National Key Research and Development Program of China (2012CB518700, 2014CB849602)
  • National Key Research and Development Program of China Stem Cell and Translational Research (2017YFA0103500)
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
Keywords
hair follicle stem cells, stem cell depletion, Piezo1, mechanosensitive ion channels, calcium signaling, TNF-α, apoptosis, aging, androgenetic alopecia, hair cycle, mechanical compression
MeSH terms
Calcium, Miniaturization, Stem Cells, Tumor Necrosis Factor-alpha, Hair Follicle

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