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Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis
Abstract
Inconsistent with the view that hair follicle stem cells reside in the matrix area of the hair bulb, we found that label-retaining cells exist exclusively in the bulge area of the mouse hair follicle. The bulge consists of a subpopulation of outer root sheath cells located in the midportion of the follicle at the arrector pili muscle attachment site. Keratinocytes in the bulge area are relatively undifferentiated ultrastructurally. They are normally slow cycling, but can be stimulated to proliferate transiently by TPA. Located in a well-protected and nourished environment, these cells mark the lower end of the "permanent" portion of the follicle. Our findings, plus a reevaluation of the literature, suggest that follicular stem cells reside in the bulge region, instead of the lower bulb. This new view provides insights into hair cycle control and the possible involvement of hair follicle stem cells in skin carcinogenesis.
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“It has been reported that slow-cycling HF stem cells reside in a bulge region of the outer root sheath located proximal to the SG (Cotsarelis et al., 1990; Lavker et al., 2003).”
From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Cotsarelis et al., 1990
In the citing paper
“Initiation of a new anagen cycle depends upon activation of a small number of quiescent stem cells that reside in the bulge, a niche at the follicle base15–19.”
From Conditional telomerase induction causes proliferation of hair follicle stem cells (2005) · cites this paper as [15]
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Metadata
- Authors
- Cotsarelis, G., Sun, T.-T., & Lavker, R. M.
- Affiliations
- University of Pennsylvania (US)
- New York University (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1990-06
- Volume
- 61
- Issue
- 7
- Pages
- 1329-1337
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1980332250
- Cited by
- 2,276
- References
- 84
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 39 · 2023: 35 · 2022: 48 · 2021: 57 · 2020: 68 · 2019: 65 · 2018: 59 · 2017: 69 · 2016: 60 · 2015: 75 · 2014: 91 · 2013: 102 · 2012: 120
- FWCI
- 56.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar034511-08, 5p01ar039674-05)
- National Eye Institute (EY 06769)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 39674, AR34511)
- Topics
- Health Sciences › Medicine › Dermatology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Dermatology › Cancer and Skin Lesions
- Keywords
- label-retaining cells, hair follicle bulge, hair follicle stem cells, pilosebaceous unit, outer root sheath, arrector pili muscle, hair cycle, skin carcinogenesis, keratinocyte proliferation
- MeSH terms
- Animals, Animals, Newborn, Cell Cycle, Cell Division, Cells, Cultured, Hair, Mice, Inbred Strains, Microscopy, Electron, Skin Neoplasms, Tetradecanoylphorbol Acetate, Thymidine, Mice
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