ArticleeLife2024
Measures of genetic diversification in somatic tissues at bulk and single-cell resolution.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Mosaic Accumulation of Somatic Genetic Variation and Estimates of Age in the Long-Lived Reef-Building Coral Acropora palmata.Molecular ecology · 2026Article
- The Evolution of Polyclonal Competition in Aging Hematopoiesis.Cancer discovery · 2026Article
- Modeling the evolutionary dynamics of clonal hematopoiesis.Nature genetics · 2026Review
- Cell State Transitions Drive the Evolution of Disease Progression in B-Lymphoblastic Leukemia.Cancer research communications · 2026Article
- Article
- Quantitative and sensitive sequencing of somatic mutations induced by a maize transposon.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Single-cell mutational burden distributions in birth-death processes.PLoS computational biology · 2025Article
- Quantifying cell divisions along evolutionary lineages in cancer.Nature genetics · 2025Article
- Reconstructing developmental lineages: a retrospective approach using somatic mutations and variant allele frequency.Frontiers in genetics · 2025Review
- Capturing the unpredictability of stem cells.eLife · 2024Article
- cloneRate: fast estimation of single-cell clonal dynamics using coalescent theory.Bioinformatics (Oxford, England) · 2023Article
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Authors and funding
4 authors.
Funding
Abstract
Intra-tissue genetic heterogeneity is universal to both healthy and cancerous tissues. It emerges from the stochastic accumulation of somatic mutations throughout development and homeostasis. By combining population genetics theory and genomic information, genetic heterogeneity can be exploited to infer tissue organization and dynamics in vivo. However, many basic quantities, for example the dynamics of tissue-specific stem cells remain difficult to quantify precisely. Here, we show that single-cell and bulk sequencing data inform on different aspects of the underlying stochastic processes. Bulk-derived variant allele frequency spectra (VAF) show transitions from growing to constant stem cell populations with age in samples of healthy esophagus epithelium. Single-cell mutational burden distributions allow a sample size independent measure of mutation and proliferation rates. Mutation rates in adult hematopietic stem cells are higher compared to inferences during development, suggesting additional proliferation-independent effects. Furthermore, single-cell derived VAF spectra contain information on the number of tissue-specific stem cells. In hematopiesis, we find approximately 2 × 10
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