ArticleNature2012
Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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Who cites it
237 citing papers in PubMed, 395 citations in OpenAlex.
- Metformin for treatment of cytopenias in children and young adults with Fanconi anemia.Blood advances · 2022Trial
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- ZMAT3 alleviates cell death in Fanconi anemia via adaptation of sphingolipid metabolism.Science advances · 2026Article
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa.medRxiv : the preprint server for health sciences · 2026Article
- Differential regulation of retinoic acid metabolism in Fanconi anemia.Scientific reports · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Insights and modulation of RNA polymerase-dependent R-loop and dsRNA in Fanconi anemia hematopoietic stem cells.JCI insight · 2026Article
- Metabolite-induced DNA damage drives stochastic stem cell loss and clonal hematopoiesis.Cell stem cell · 2026Article
- Tissue-specific mutagenesis from endogenous guanine damage is suppressed by Polκ and DNA repair.Nature communications · 2025Article
- Structural Isomer Cumulative molecular fingerprinting method (SIC) for standardizing structural isomeric relationships.Communications chemistry · 2025Article
- Genotoxic formaldehyde and lipid aldehydes are sources of DNA damage in keratinocytes.bioRxiv : the preprint server for biology · 2025Article
- Dynamics of Fanconi anemia protein D2 in association with nuclear lipid droplet formation.Journal of cell science · 2025Article
- Mechanistic insights into alcohol-induced DNA crosslink repair by Slx4-Xpf-Ercc1 nuclease complex in the Fanconi anaemia pathway.Communications biology · 2025Article
- DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs.Nucleic acids research · 2025Article
- Article
- ALDH9A1 deficiency as a source of endogenous DNA damage that requires repair by the Fanconi anemia pathway.The Journal of cell biology · 2025Article
- Distinct developmental outcomes in DNA repair-deficient FANCC c.67delG mutant and FANCCCell death and differentiation · 2025Article
- Deficiency of the Fanconi anemia core complex protein FAAP100 results in severe Fanconi anemia.The Journal of clinical investigation · 2025Article
- Key Ferroptosis Genes and their Predictive and Diagnostic Value in Fanconi Anemia.Physiological research · 2025Article
177 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Haematopoietic stem cells (HSCs) regenerate blood cells throughout the lifespan of an organism. With age, the functional quality of HSCs declines, partly owing to the accumulation of damaged DNA. However, the factors that damage DNA and the protective mechanisms that operate in these cells are poorly understood. We have recently shown that the Fanconi anaemia DNA-repair pathway counteracts the genotoxic effects of reactive aldehydes. Mice with combined inactivation of aldehyde catabolism (through Aldh2 knockout) and the Fanconi anaemia DNA-repair pathway (Fancd2 knockout) display developmental defects, a predisposition to leukaemia, and are susceptible to the toxic effects of ethanol-an exogenous source of acetaldehyde. Here we report that aged Aldh2(-/-) Fancd2(-/-) mutant mice that do not develop leukaemia spontaneously develop aplastic anaemia, with the concomitant accumulation of damaged DNA within the haematopoietic stem and progenitor cell (HSPC) pool. Unexpectedly, we find that only HSPCs, and not more mature blood precursors, require Aldh2 for protection against acetaldehyde toxicity. Additionally, the aldehyde-oxidizing activity of HSPCs, as measured by Aldefluor stain, is due to Aldh2 and correlates with this protection. Finally, there is more than a 600-fold reduction in the HSC pool of mice deficient in both Fanconi anaemia pathway-mediated DNA repair and acetaldehyde detoxification. Therefore, the emergence of bone marrow failure in Fanconi anaemia is probably due to aldehyde-mediated genotoxicity restricted to the HSPC pool. These findings identify a new link between endogenous reactive metabolites and DNA damage in HSCs, and define the protective mechanisms that counteract this threat.
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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.