Evidence map›Paper›PMID 41875892›Full record

ArticleCell stem cell2026

Metabolite-induced DNA damage drives stochastic stem cell loss and clonal hematopoiesis.

Ashley N Kamimae-Lanning, Jill M Brown, Matthias Günther, Franziska Esau, Holly Russell, Lise Larcher, Frédéric Langevin, Tomoya Isobe, Nicola K Wilson, Felix A Dingler and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Ashley N Kamimae-LanningUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Jill M BrownUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Matthias GüntherDivision of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany.
Franziska EsauDivision of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany.
Holly RussellUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Lise LarcherInstitut de Recherche Saint-Louis (IRSL), Université Paris Cité, 75010 Paris, France; INSERM UMR1342 CNRS EMR8000, Paris, France; Saint Louis Hospital, Hematology Laboratory, APHP, Paris, France; Centre de Référence Maladies Rares "Aplasie Médullaire", Saint-Louis and Robert Debré Hospitals, Paris, France.
Frédéric LangevinMRC Laboratory of Molecular Biology, Cambridge, UK.
Tomoya IsobeCambridge Stem Cell Institute, Department of Haematology, University of Cambridge, Cambridge, UK.
Nicola K WilsonCambridge Stem Cell Institute, Department of Haematology, University of Cambridge, Cambridge, UK.
Felix A DinglerUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Rebecca L CordellCentre for Environmental Health and Sustainability, The University of Leicester, Leicester, UK.
Meng WangDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA; Department of Haematology, Addenbrooke's Hospital, Cambridge, UK.
Christopher L MillingtonUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Nina ClaudinoDivision of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany.
Ewa GogolaUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Matthew NichollsUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Verena KörberUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Berthold GöttgensCambridge Stem Cell Institute, Department of Haematology, University of Cambridge, Cambridge, UK.
Marella F T R de BruijnUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK.
Juan I GaraycoecheaHubrecht Institute, Utrecht, the Netherlands.
Jean SoulierInstitut de Recherche Saint-Louis (IRSL), Université Paris Cité, 75010 Paris, France; INSERM UMR1342 CNRS EMR8000, Paris, France; Saint Louis Hospital, Hematology Laboratory, APHP, Paris, France; Centre de Référence Maladies Rares "Aplasie Médullaire", Saint-Louis and Robert Debré Hospitals, Paris, France.
Thomas HöferDivision of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany. Electronic address: t.hoefer@dkfz.de.
Ketan J PatelUniversity of Oxford, MRC Weatherall Institute of Molecular Medicine, Molecular Haematology Unit, Oxford, UK. Electronic address: ketan.patel@imm.ox.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA damage and mutations in hematopoietic stem cells (HSCs) enable clonal hematopoiesis (CH). Such damage occurs across a lifetime, but its origins remain unknown. Here, we demonstrate that endogenous formaldehyde causes HSC attrition and subsequently CH. We generated conditional mouse models lacking formaldehyde detoxification and Fanconi anemia (FA) DNA repair in blood. Formaldehyde protection was crucial for embryonic HSC emergence and throughout life. Despite severe deficiencies in HSCs, these mice produced blood for many months. To determine what enables this, we employed an unbiased method for detecting clones, which exploits somatic variant data. This revealed initial polyclonal hematopoiesis that diminishes to monoclonal hematopoiesis, devoid of known genetic selection. Furthermore, in FA children, we find the same transition to monoclonal hematopoiesis. Therefore, DNA damage-induced attrition down to the last functional cell can be a driving force for CH, representing an alternative route to CH other than purely by fitness-enhancing selection.

Indexed as

Clonal HematopoiesisDNA DamageFormaldehydeHematopoiesisHematopoietic Stem CellsAnimalsDNA RepairFanconi AnemiaHumansMiceStochastic ProcessesFormaldehydebone marrow failureclonal hematopoiesisendogenous DNA damageFanconi anemiaformaldehydeHSC attritionneutral driftsomatic evolutionstem cell aging

Identifiers

PMID41875892
PMCPMC7619061

What OpenQuestion holds

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Registered trials

None linked

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.