Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging
Open accessAbstract
Werner syndrome (WS) patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs) and neural stem/progenitor cells (NPCs). We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this "aging" discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells.
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Mesenchymal stem cells, but not neural stem cells, reprogrammed from Werner syndrome iPSCs show premature cellular senescence.
“Mesenchymal stem cells, but not neural stem cells, reprogrammed from Werner syndrome iPSCs show premature cellular senescence189.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [189]
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- Authors
- Cheung, H.-H., Liu, X., Canterel-Thouennon, L., Li, L., Edmonson, C., & Rennert, O. M.
- Affiliations
- National Institutes of Health (US)
- Chinese University of Hong Kong (HK)
- Corresponding author
- Cheung, Hoi-Hung
- Rennert, Owen M.
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 2
- Issue
- 4
- Pages
- 534-546
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC3986587
- OpenAlex
- W2138809668
- Cited by
- 102
- References
- 52
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 11 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 20 · 2015: 9 · 2014: 3
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- 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 › Pluripotent Stem Cells Research
- Keywords
- Werner syndrome, telomerase, premature aging, telomere dysfunction, mesenchymal stem cells, neural stem/progenitor cells, premature senescence, telomere shortening, hTERT, p53, DNA damage sensitivity, induced pluripotent stem cells, fibroblast reprogramming
- MeSH terms
- Cell Differentiation, DNA Damage, Fibroblasts, Humans, Stem Cells, Werner Syndrome, Cluster Analysis, Tumor Suppressor Protein p53, Cellular Senescence, Cell Lineage, Telomerase, Gene Expression Profiling, Cell Proliferation, Induced Pluripotent Stem Cells, Neural Stem Cells, Mesenchymal Stem Cells, Cellular Reprogramming
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