ArticleNature genetics2022
Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder.Cell genomics · 2025Pooled it
- Clonal hematopoiesis is associated with protection from Alzheimer's disease.Nature medicine · 2023Pooled it
- A guide to understanding tumour evolution through the lens of population genetics.Nature reviews. Cancer · 2026Review
- A single-cell lens into the co-evolution of genotypes and phenotypes in cancer.Nature reviews. Cancer · 2026Review
- Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming.Nature communications · 2026Article
- The Evolution of Polyclonal Competition in Aging Hematopoiesis.Cancer discovery · 2026Article
- Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Clonal hematopoiesis of indeterminate potential and metabolic dysfunction-associated steatotic liver disease: Korean biopsy cohort.Hepatology international · 2026Article
- Single-nucleus multimodal spatial transcriptomics reveals spatial colocalization of neoantigen-expressing tumor cells and cognate T cells.Nature biotechnology · 2026Article
- Patterns and drivers of 43,617 mosaic chromosomal alterations in blood.Nature genetics · 2026Article
- Multi-omics approaches reveal erythroid progenitor cell in cancer: from passive bystander to active player.Oncogene · 2026Review
- Mutation-specific impairment of TET2 and DNMT3A enzymatic activity predicts clonal hematopoiesis disease risk.medRxiv : the preprint server for health sciences · 2026Article
- DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency.Cancer discovery · 2026Article
- Early Driver, Late Bystander: Stage-Specific Roles of DNMT3A R882 Mutations Unveiled in Human AML.Cancer discovery · 2026Article
- Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes.Nature medicine · 2026Article
- Review
- DNMT3A p.R882C driven proliferation and anti-apoptotic effects in pancreatic cancer cells.Scientific reports · 2026Article
- Clonal Hematopoiesis and Incident Heart Failure.JAMA cardiology · 2026Article
- Co-mapping clonal and transcriptional heterogeneity in somatic evolution via GoT-Multi.Cell genomics · 2026Article
- Local Promoter Methylation Disorder algorithm reveals bidirectional epigenetic disruption in DNMT3A-mutated AML and predicts azacitidine treatment response.Frontiers in oncology · 2026Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Somatic mutations in cancer genes have been detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, because mutated and wild-type cells are admixed, we have limited ability to link genotypes with phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing genotype, transcriptomes and methylomes in progenitors from individuals with DNMT3A R882 mutated clonal hematopoiesis. DNMT3A mutations result in myeloid over lymphoid bias, and an expansion of immature myeloid progenitors primed toward megakaryocytic-erythroid fate, with dysregulated expression of lineage and leukemia stem cell markers. Mutated DNMT3A leads to preferential hypomethylation of polycomb repressive complex 2 targets and a specific CpG flanking motif. Notably, the hypomethylation motif is enriched in binding motifs of key hematopoietic transcription factors, serving as a potential mechanistic link between DNMT3A mutations and aberrant transcriptional phenotypes. Thus, single-cell multi-omics paves the road to defining the downstream consequences of mutations that drive clonal mosaicism.
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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.