Evidence map›Paper›PMID 38917807›Full record

ArticleCell stem cell2024

Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging.

Niels Asger Jakobsen, Sven Turkalj, Andy G X Zeng, Bilyana Stoilova, Marlen Metzner, Susann Rahmig, Murtaza S Nagree, Sayyam Shah, Rachel Moore, Batchimeg Usukhbayar and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
–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

92 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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  4. Clonal blood reshapes its home.Nature immunology · 2026
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32 more citing papers are in PubMed but not listed here.

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

30 authors.

Niels Asger JakobsenMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
Sven TurkaljMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
Andy G X ZengPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Bilyana StoilovaMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Marlen MetznerMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Susann RahmigMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Murtaza S NagreePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Sayyam ShahPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Rachel MooreMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Batchimeg UsukhbayarMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Mirian Angulo SalazarMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Grigore-Aristide GafencuMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Alison KennedyMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Simon NewmanNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Benjamin J L KendrickNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Adrian H TaylorNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Rasheed Afinowi-LuitzNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Roger GundleNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Bridget WatkinsNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Kim WhewayNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Debra BeazleyNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Alex MurisonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Alicia G Aguilar-NavarroUnidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Eugenia Flores-FigueroaUnidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Stephanie G DakinNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Andrew J CarrNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Claus NerlovMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
John E DickPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Stephanie Z XiePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Paresh VyasMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: paresh.vyas@imm.ox.ac.uk.

Funding

Medical Research Council MR/R002258/1
6 · The paper itself

Abstract

Clonal hematopoiesis (CH) arises when hematopoietic stem cells (HSCs) acquire mutations, most frequently in the DNMT3A and TET2 genes, conferring a competitive advantage through mechanisms that remain unclear. To gain insight into how CH mutations enable gradual clonal expansion, we used single-cell multi-omics with high-fidelity genotyping on human CH bone marrow (BM) samples. Most of the selective advantage of mutant cells occurs within HSCs. DNMT3A- and TET2-mutant clones expand further in early progenitors, while TET2 mutations accelerate myeloid maturation in a dose-dependent manner. Unexpectedly, both mutant and non-mutant HSCs from CH samples are enriched for inflammatory and aging transcriptomic signatures, compared with HSCs from non-CH samples, revealing a non-cell-autonomous effect. However, DNMT3A- and TET2-mutant HSCs have an attenuated inflammatory response relative to wild-type HSCs within the same sample. Our data support a model whereby CH clones are gradually selected because they are resistant to the deleterious impact of inflammation and aging.

Indexed as

AgingClonal HematopoiesisDioxygenasesDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AHematopoietic Stem CellsInflammationMutationDNA-Binding ProteinsHematopoiesisHumansProto-Oncogene ProteinsDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanProto-Oncogene ProteinsTET2 protein, humanagingclonal competitionclonal hematopoiesisDNMT3Ahematopoietic stem cellssingle-cell genomicssingle-cell RNA-seqsomatic mosaicismTET2

Identifiers

PMID38917807
PMCPMC11512683

What OpenQuestion holds

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Registered trials

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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.