Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
Open accessAbstract
Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse, yet divide every day. We now demonstrate biochemically that primary isolated Lgr5+ve stem cells contain significant telomerase activity. Telomerase activity rapidly decreases in the undifferentiated progeny of these stem cells and is entirely lost in differentiated villus cells. Conversely, asymmetric segregation of chromosomes has been proposed as a mechanism for stem cells to protect their genomes against damage. We determined the average cell cycle length of Lgr5+ve stem cells at 21.5 h and find that Lgr5+ve intestinal stem cells randomly segregate newly synthesized DNA strands, opposing the 'immortal strand' hypothesis.
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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 [138]
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References 34 · Cited by 217
- Authors
- Schepers, A. G., Vries, R., van den Born, M., van de Wetering, M., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- Corresponding author
- Clevers, Hans
- Venue
- The EMBO Journal
- Published
- 2011-02-04
- Volume
- 30
- Issue
- 6
- Pages
- 1104-1109
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3061032
- OpenAlex
- W1874198492
- Cited by
- 217
- References
- 34
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 12 · 2021: 11 · 2020: 14 · 2019: 6 · 2018: 15 · 2017: 6 · 2016: 15 · 2015: 16 · 2014: 18 · 2013: 30 · 2012: 25
- FWCI
- 19.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Lgr5, intestinal stem cells, telomerase activity, chromosome segregation, cell cycle duration, stem cell self-renewal, genome stability, intestinal crypts, villus cells, DNA replication
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Epithelial Cells, Intestinal Mucosa, Stem Cells, Time Factors, Telomerase, Chromosome Segregation, Mice, Stem Cell Niche
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