Hair shaft miniaturization causes stem cell depletion through mechanosensory signals mediated by a Piezo1-calcium-TNF-α axis
Open accessAbstract
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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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”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [83]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [83]
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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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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