The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation
Abstract
The maintenance of genome integrity in stem cells (SCs) is critical for preventing cancer formation and cellular senescence. The immortal strand hypothesis postulates that SCs protect their genome by keeping the same DNA strand throughout life by asymmetrical cell divisions, thus avoiding accumulation of mutations that can arise during DNA replication. The in vivo relevance of this model remains to date a matter of intense debate. In this study, we revisited this long-standing hypothesis, by analyzing how multipotent hair follicle (HF) SCs segregate their DNA strands during morphogenesis, skin homeostasis, and SC activation. We used three different in vivo approaches to determine how HF SCs segregate their DNA strand during cell divisions. Double-labeling studies using pulse-chase experiments during morphogenesis and the first adult hair cycle showed that HF SCs incorporate two different nucleotide analogs, contradictory to the immortal strand hypothesis. The co-segregation of DNA and chromatin labeling during pulse-chase experiments demonstrated that label retention in HF SCs is rather a mark of relative quiescence. Moreover, DNA labeling of adult SCs, similar to labeling during morphogenesis, also resulted in label retention in HF SCs, indicating that chromosome segregation occurs randomly in most of these cells. Altogether, our results demonstrate that DNA strand segregation occurs randomly in the majority of HF SCs during development, tissue homeostasis, and following SC activation. Disclosure of potential conflicts of interest is found at the end of this article.
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Evidence of asymmetric chromosome segregation was lacking in certain studies of epidermal stem cells and ISCs.
“evidence of asymmetric chromosome segregation was lacking in certain studies of epidermal stem cells136,137 and ISCs138.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [136]
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- Authors
- Sotiropoulou, P. A., Candi, A., & Blanpain, C.
- Affiliations
- Université Libre de Bruxelles (BE)
- Corresponding author
- Blanpain, Cédric
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09-04
- Volume
- 26
- Issue
- 11
- Pages
- 2964-2973
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2024790458
- Cited by
- 67
- References
- 36
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 14 · 2012: 12
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- Schlumberger Foundation
- Fonds De La Recherche Scientifique - FNRS
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- asymmetric cell division, epidermal stem cells, hair follicle stem cells, genome stability, stem cell quiescence, label retention, pulse-chase labeling, hair follicle morphogenesis, skin homeostasis, stem cell activation
- MeSH terms
- Epidermal Cells, Animals, Cell Division, Chromatin, DNA Damage, Keratinocytes, Hair Follicle, Chromosome Segregation, Multipotent Stem Cells, Mice
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