A Two-Step Mechanism for Stem Cell Activation during Hair Regeneration
Open accessAbstract
Hair follicles (HFs) undergo cyclic bouts of degeneration, rest, and regeneration. During rest (telogen), the hair germ (HG) appears as a small cell cluster between the slow-cycling bulge and dermal papilla (DP). Here we show that HG cells are derived from bulge stem cells (SCs) but become responsive quicker to DP-promoting signals. In vitro, HG cells also proliferate sooner but display shorter-lived potential than bulge cells. Molecularly, they more closely resemble activated bulge rather than transit-amplifying (matrix) cells. Transcriptional profiling reveals precocious activity of both HG and DP in late telogen, accompanied by Wnt signaling in HG and elevated FGFs and BMP inhibitors in DP. FGFs and BMP inhibitors participate with Wnts in exerting selective and potent stimuli to the HG both in vivo and in vitro. Our findings suggest a model where HG cells fuel initial steps in hair regeneration, while the bulge is the engine maintaining the process.
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The mesenchymal niche of the hair follicle provides molecular signals that are sufficient to induce hair growth.
“It was demonstrated in a study of HFSCs that the mesenchymal niche of the hair follicle provides molecular signals that are sufficient to induce hair growth [86].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [86]
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Self-citation
- Authors
- Greco, V., Chen, T., Rendl, M., Schober, M., Pasolli, H. A., Stokes, N., dela Cruz-Racelis, J., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 4
- Issue
- 2
- Pages
- 155-169
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2668200
- OpenAlex
- W1992972287
- Cited by
- 800
- References
- 44
- Citations by year
- 2026: 28 · 2025: 45 · 2024: 52 · 2023: 48 · 2022: 61 · 2021: 45 · 2020: 53 · 2019: 49 · 2018: 48 · 2017: 53 · 2016: 41 · 2015: 49 · 2014: 51 · 2013: 48 · 2012: 51
- FWCI
- 50.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (2r01ar050452-21)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR031737, R01AR063663, R01-AR050452)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- hair regrowth, hair follicle, hair germ, bulge stem cells, dermal papilla, stem cell activation, Wnt signaling, FGF signaling, BMP inhibitors, telogen, hair cycle, stem cell differentiation, hair matrix cells
- MeSH terms
- Animals, Cells, Cultured, Female, Mice, Transgenic, Morphogenesis, Regeneration, Stem Cells, Transcription, Genetic, Signal Transduction, Hair Follicle, Cell Lineage, Wnt Proteins, beta Catenin, Mice, Fibroblast Growth Factor 7
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