ArticleProceedings of the National Academy of Sciences of the United States of America2019
Single-cell whole-genome sequencing reveals the functional landscape of somatic mutations in B lymphocytes across the human lifespan.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma.Scientific reports · 2021Pooled it
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- Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.Science China. Life sciences · 2026Article
- Somatic mutations and genome mosaicism in aging and disease.Experimental & molecular medicine · 2026Review
- DREAM repressive activity links somatic mutation, lifespan and disease.Nature aging · 2026Article
- The aging genome exhibits organized vulnerability to somatic mutations.bioRxiv : the preprint server for biology · 2026Article
- DIAG: A Framework for Evaluating Whole-Genome Amplification Quality in Single-Cell SNV Analysis.Biology · 2026Article
- Unravelling genome-wide mosaic microsatellite mutations at single-cell resolution.bioRxiv : the preprint server for biology · 2026Article
- SomaMutDB 2.0: A comprehensive database for exploring somatic mutations and their functional impact in normal human tissues.Nucleic acids research · 2026Article
- Accurate detection of somatic single-nucleotide variants from bulk RNA-seq data using RNA-MosaicHunter.Nucleic acids research · 2026Article
- Reconstructing the lifelong history of cells and tissues via somatic mutation analysis.Cellular and molecular life sciences : CMLS · 2025Review
- Single-cell analysis of the somatic mutational landscape in human chondrocytes during aging and in osteoarthritis.Nature aging · 2025Article
- Review
- Autonomous AI Agents Discover Aging Interventions from Millions of Molecular Profiles.bioRxiv : the preprint server for biology · 2025Article
- Large-scale single-cell phylogenetic mapping of clonal evolution in the human aging esophagus.bioRxiv : the preprint server for biology · 2025Article
- Divergent accumulation patterns of SNVs and INDELs reveal negative selection in noncancerous cells.Innovation (Cambridge (Mass.)) · 2025Article
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- Role of intratumoral heterogeneity in metastatic progression and drug resistance.Discover oncology · 2025Review
- Consistent asymmetry in DNA damage artefacts across target regions in exome sequencing data.NAR genomics and bioinformatics · 2025Article
84 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Accumulation of mutations in somatic cells has been implicated as a cause of aging since the 1950s. However, attempts to establish a causal relationship between somatic mutations and aging have been constrained by the lack of methods to directly identify mutational events in primary human tissues. Here we provide genome-wide mutation frequencies and spectra of human B lymphocytes from healthy individuals across the entire human lifespan using a highly accurate single-cell whole-genome sequencing method. We found that the number of somatic mutations increases from <500 per cell in newborns to >3,000 per cell in centenarians. We discovered mutational hotspot regions, some of which, as expected, were located at Ig genes associated with somatic hypermutation (SHM). B cell-specific mutation signatures associated with development, aging, or SHM were found. The SHM signature strongly correlated with the signature found in human B cell tumors, indicating that potential cancer-causing events are already present even in B cells of healthy individuals. We also identified multiple mutations in sequence features relevant to cellular function (i.e., transcribed genes and gene regulatory regions). Such mutations increased significantly during aging, but only at approximately one-half the rate of the genome average, indicating selection against mutations that impact B cell function. This full characterization of the landscape of somatic mutations in human B lymphocytes indicates that spontaneous somatic mutations accumulating with age can be deleterious and may contribute to both the increased risk for leukemia and the functional decline of B lymphocytes in the elderly.
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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.