ArticleThe Journal of clinical investigation2012
Aneuploidy as a mechanism for stress-induced liver adaptation.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 192 citations in OpenAlex.
- SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues.Cell stem cell · 2026Article
- Diploid hepatocytes resist acetaminophen-induced liver injury through suppressed JNK signaling.Cell death & disease · 2026Article
- Etiology of polyploid giant cancer cells: a new frontier in cancer biology.Cancer cell international · 2026Review
- How Do Cancer Cells Fuse and Why?Advances in experimental medicine and biology · 2026Review
- The Ploidy State as a Determinant of Hepatocyte Proliferation.Seminars in liver disease · 2023Review
- The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics.Scientific reports · 2023Article
- Diverse microtubule-targeted anticancer agents kill cells by inducing chromosome missegregation on multipolar spindles.PLoS biology · 2023Article
- Cellular polyploidy in organ homeostasis and regeneration.Protein & cell · 2023Article
- Regenerative potential of multinucleated cells: bone marrow adiponectin-positive multinucleated cells take the lead.Stem cell research & therapy · 2023Article
- Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death.Nature communications · 2023Article
- Single-cell resolved ploidy and chromosomal aberrations in nonalcoholic steatohepatitis-(NASH) induced hepatocellular carcinoma and its precursor lesions.Scientific reports · 2022Article
- Reducing the aneuploid cell burden - cell competition and the ribosome connection.Disease models & mechanisms · 2022Review
- Inhibition of polyploidization in Pten-deficient livers reduces steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2022Article
- Implications of Polyploidy and Ploidy Alterations in Hepatocytes in Liver Injuries and Cancers.International journal of molecular sciences · 2022Review
- Polyploidy in development and tumor models in Drosophila.Seminars in cancer biology · 2022Review
- Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness.Nature communications · 2022Article
- Single-Cell DNA Sequencing Reveals Chromosomal Diversity in HCC and a Novel Model of HCC Evolution.Gastroenterology · 2022Article
- Low adipocyte hepatocellular carcinoma is associated with aggressive cancer biology and with worse survival.American journal of cancer research · 2022Article
- Chromosome instability and aneuploidy as context-dependent activators or inhibitors of antitumor immunity.Frontiers in immunology · 2022Review
- Genetic and Cellular Contributions to Liver Regeneration.Cold Spring Harbor perspectives in biology · 2021Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Over half of the mature hepatocytes in mice and humans are aneuploid and yet retain full ability to undergo mitosis. This observation has raised the question of whether this unusual somatic genetic variation evolved as an adaptive mechanism in response to hepatic injury. According to this model, hepatotoxic insults select for hepatocytes with specific numerical chromosome abnormalities, rendering them differentially resistant to injury. To test this hypothesis, we utilized a strain of mice heterozygous for a mutation in the homogentisic acid dioxygenase (Hgd) gene located on chromosome 16. Loss of the remaining Hgd allele protects from fumarylacetoacetate hydrolase (Fah) deficiency, a genetic liver disease model. When adult mice heterozygous for Hgd and lacking Fah were exposed to chronic liver damage, injury-resistant nodules consisting of Hgd-null hepatocytes rapidly emerged. To determine whether aneuploidy played a role in this phenomenon, array comparative genomic hybridization (aCGH) and metaphase karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically enriched in all mice that became completely resistant to tyrosinemia-induced hepatic injury. The frequency of chromosome 16-specific aneuploidy was approximately 50%. This result indicates that selection of a specific aneuploid karyotype can result in the adaptation of hepatocytes to chronic liver injury. The extent to which aneuploidy promotes hepatic adaptation in humans remains under investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.