Hepatocytes with extensive telomere deprotection and fusion remain viable and regenerate liver mass through endoreduplication
Open accessAbstract
We report that mouse liver cells are highly resistant to extensive telomere dysfunction. In proliferating cells, telomere dysfunction results in chromosome end fusions, a DNA damage signal, and apoptosis or senescence. To determine the consequences of telomere dysfunction in noncycling cells, we used conditional deletion of the telomeric protein TRF2 in hepatocytes. TRF2 loss resulted in telomeric accumulation of γ-H2AX and frequent telomere fusions, indicating telomere deprotection. However, there was no induction of p53 or apoptosis, and liver function appeared unaffected. Furthermore, the loss of TRF2 did not compromise liver regeneration after partial hepatectomy. Remarkably, liver regeneration occurred without cell division involving endoreduplication and cell growth, thereby circumventing the chromosome segregation problems associated with telomere fusions. We conclude that nondividing hepatocytes can maintain and regenerate liver function despite substantial loss of telomere integrity.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Telomere deprotection and infection by HBV or HCV promote polyploidisation via unknown mechanisms.
“Telomere deprotection162 and infection by HBV or HCV163,164 were also reported to promote polyploidisation via unknown mechanisms.”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [162]
The Conclusions (page not provided) report that TRF2-deficient hepatocytes become highly polyploid, supporting the telomere-deprotection part of the claim. But the paper describes a mechanism—joined telomeres prevent chromatid segregation, while repeated DNA replication continues—so it does not support describing that mechanism as unknown. The HBV/HCV part is attached to other citations and is not judged here. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 22 · Cited by 116
- Authors
- Lazzerini Denchi, E., Celli, G., & de Lange, T.
- Affiliations
- Rockefeller University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-10-01
- Volume
- 20
- Issue
- 19
- Pages
- 2648-2653
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1578691
- OpenAlex
- W4232108342
- Cited by
- 116
- References
- 22
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 11 · 2019: 4 · 2018: 9 · 2017: 12 · 2016: 4 · 2015: 7 · 2014: 3 · 2013: 8 · 2012: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- National Institutes of Health (GM49046)
- National Institute on Aging (R56AG016642, AG16642, R01AG016642)
- National Institute of General Medical Sciences (GM 49046, R37GM049046, R01GM049046)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- telomere dysfunction, telomere fusion, TRF2, hepatocytes, liver regeneration, endoreduplication, partial hepatectomy, γH2AX, p53, apoptosis, cellular senescence, chromosome segregation
- MeSH terms
- Animals, DNA Damage, Female, Liver, Liver Regeneration, Male, Mice, Transgenic, Tumor Suppressor Protein p53, Telomere, Cellular Senescence, Apoptosis, In Situ Hybridization, Fluorescence, Mice, Knockout, Hepatocytes, Telomeric Repeat Binding Protein 2, Cell Proliferation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
