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Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification
Abstract
The transcription factor Myc (c-Myc) plays an important role in cell growth and cell death, yet its physiological function remains unclear. Ectopic activation of Myc has been recently suggested to regulate cell mass, and Drosophila dmyc controls cellular growth and size independently of cell division. By contrast, it has been proposed that in mammals Myc controls cell division and cell number. To gain insights into this debate we have specifically knocked out Myc in epidermis. Myc epidermal knockout mice are viable and their keratinocytes continue to cycle, but they display severe skin defects. The skin is tight and fragile, tears off in areas of mechanical friction and displays impaired wound healing. Steady-state epidermis is thinner, with loss of the proliferative compartment and premature differentiation. Remarkably, keratinocyte cell size, growth and endoreplication are reduced, and stem cell amplification is compromised. The results provide new and direct evidence for a role for endogenous Myc in cellular growth that is required for hyperproliferative cycles and tissue homeostasis.
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“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 [38]
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Metadata
- Authors
- Zanet, J., Pibre, S., Jacquet, C., Ramirez, A., de Alborán, I. M., & Gandarillas, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Epithelial Damage, Repair and Tissue Engineering Program, CIEMAT, Madrid, Spain
- Centro Nacional de Biotecnologia, CSIC, Madrid, Spain
- Corresponding author
- Gandarillas, Alberto
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2005-04-15
- Volume
- 118
- Issue
- 8
- Pages
- 1693-1704
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2101568666
- Cited by
- 123
- References
- 50
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 8 · 2012: 8
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › 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, epidermis, keratinocytes, cell size, cell growth, endoreplication, hyperproliferation, epidermal stem cells, wound healing, skin defects, tissue homeostasis, cell differentiation
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Cell Division, Cell Movement, Epidermis, Female, Homeostasis, Male, Mice, Transgenic, Ploidies, Stem Cells, Stress, Mechanical, Wound Healing, Keratinocytes, Proto-Oncogene Proteins c-myc, Mice, Knockout, Hair Follicle, Cell Size, Cell Enlargement, Cell Proliferation, Mice
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