c-Myc promotes differentiation of human epidermal stem cells
Open accessAbstract
The epidermis contains two types of proliferative keratinocyte: stem cells, with unlimited self-renewal capacity, and transit amplifying cells, those daughters of stem cells that are destined to withdraw from the cell cycle and terminally differentiate after a few rounds of division. In a search for factors that regulate exit from the stem cell compartment, we constitutively expressed c-Myc in primary human keratinocytes by use of wild-type and steroid-activatable constructs. In contrast to its role in other cell types, activation of c-Myc in keratinocytes caused a progressive reduction in growth rate, without inducing apoptosis, and a marked stimulation of terminal differentiation. Keratinocytes can be enriched for stem or transit amplifying cells on the basis of β 1 integrin expression and by use of this method to fractionate cells prior to c-Myc activation, we found that c-Myc acted selectively on stem cells, driving them into the transit amplifying compartment. As a result, activation of c-Myc in epidermis reconstituted on a dermal equivalent led to premature execution of the differentiation program. The transcriptional regulatory domain of c-Myc was required for these effects because a deletion within that domain acted as a dominant-negative mutation. Our results reveal a novel biological role for c-Myc and provide new insights into the mechanism regulating epidermal stem cell fate.
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Deregulated c-Myc expression depletes epidermal stem cells by making the cells overproliferate, move out of their niche, and then differentiate.
“Deregulated c-Myc expression was shown to deplete ESCs by making the ESCs overproliferate, move out of their niche, and then differentiate [89, 90].”
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 [90]
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- Authors
- Gandarillas, A., & Watt, F. M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1997-11-01
- Volume
- 11
- Issue
- 21
- Pages
- 2869-2882
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316650
- OpenAlex
- W2116562692
- Cited by
- 326
- References
- 65
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 9 · 2013: 14 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- European Commission
- 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 › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- c-Myc, epidermal stem cells, keratinocyte differentiation, terminal differentiation, transit amplifying cells, stem cell self-renewal, beta1 integrin, dominant negative mutation, dermal equivalent
- MeSH terms
- Epidermal Cells, Adult, Animals, Breast, Cell Differentiation, Cell Division, Cells, Cultured, DNA, Epidermis, Female, Genetic Vectors, Histones, Humans, Infant, Newborn, Kinetics, Male, Recombinant Proteins, Retroviridae, Skin, Stem Cells, Transcription, Genetic, Transfection, Keratinocytes, Proto-Oncogene Proteins c-myc, 3T3 Cells, Sequence Deletion, Mice
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