c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny
Open accessAbstract
Background The epidermis is maintained throughout adult life by pluripotential stem cells that give rise, via daughter cells of restricted self-renewal capacity and high differentiation probability (transit-amplifying cells), to interfollicular epidermis, hair follicles, and sebaceous glands. In vivo, transit-amplifying cells are actively cycling, whereas stem cells divide infrequently. Experiments with cultured human keratinocytes suggest that c-Myc promotes epidermal-stem cell differentiation. However, Myc is a potent oncogene that suppresses differentiation and causes reversible neoplasia when expressed in the differentiating epidermal layers of transgenic mice. To investigate the effects of c-Myc on the stem cell compartment in vivo, we targetted c-MycER to the basal layer of transgenic mouse epidermis. Results The activation of c-Myc by the application of 4-hydroxy-tamoxifen caused progressive and irreversible changes in adult epidermis. Proliferation was stimulated, but interfollicular keratinocytes still underwent normal terminal differentiation. Hair follicles were abnormal, and sebaceous differentiation was stimulated at the expense of hair differentiation. The activation of c-Myc by a single application of 4-hydroxy-tamoxifen was as effective as continuous treatment in stimulating proliferation and sebocyte differentiation, and the c-Myc-induced phenotype continued to develop even after the grafting of treated skin to an untreated recipient. Conclusions We propose t…
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c-Myc is a fundamental factor that governs sebaceous gland expansion in vivo.
“A fundamental factor that governs SG expansion in vivo is c-Myc3, 29–31,.”
From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [29]
Prior findings show that overexpression of c-Myc leads to enhanced SG expansion, while conditional deletion of c-Myc results in decreased SG size, cell proliferation, and sebocyte differentiation.
“previously reported findings where overexpression of c-Myc led to enhanced SG expansion, while conditional deletion of c-Myc resulted in decreased SG size, cell proliferation, and sebocyte differentiation3, 29, 38, 39.”
From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [29]
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- Authors
- Arnold, I., & Watt, F. M.
- Corresponding author
- Watt, Fiona M
- ORCID
- Watt, Fiona M
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 11
- Issue
- 8
- Pages
- 558-568
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2059694060
- Cited by
- 341
- References
- 0
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 11 · 2013: 16 · 2012: 15
- FWCI
- 23.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Molecular Biology Organization
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- c-Myc, epidermal stem cells, transit amplifying cells, keratinocyte differentiation, sebaceous gland differentiation, hair follicle differentiation, epidermal proliferation, 4-hydroxytamoxifen, epidermis
- MeSH terms
- Epidermal Cells, Animals, Cell Differentiation, Cell Movement, Female, Humans, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Stem Cells, Proto-Oncogene Proteins c-myc, Hair Follicle, Mice
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