ArticleNature methods2025
High-resolution, noninvasive single-cell lineage tracing in mice and humans based on DNA methylation epimutations.
Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Computational approaches for multimodal lineage tracing.Nature reviews. Genetics · 2026Review
- Article
- A new era of lineage tracing.Cell research · 2026Article
- Spatio-DARLIN enables robust and efficient in situ lineage tracing in mice at single-cell resolution.Nature methods · 2026Article
- Long-read sequencing of single cell-derived melanoma sublines reveals divergent and parallel genomic and epigenomic evolutionary trajectories.Nature communications · 2026Article
- Lineage tracing from cellular heritage to disease destiny.Nature genetics · 2026Review
- Charting single-cell lineages with synthetic and natural barcodes.Nature reviews. Genetics · 2026Review
- Reading cell division histories from the methylome.Nature reviews. Genetics · 2026Article
- Recurrence in the chemotherapy regimen of bladder carcinoma originates from quiescent epidermoid-like cells.Nature communications · 2026Article
- MiTo: tracing the phenotypic evolution of somatic cell lineages via mitochondrial single-cell multi-omics.Nature communications · 2026Article
- The Use of Single-Cell Mitochondrial DNA SNP Combinations for Distinguishing Organ-Specific Cell Types.Cells · 2026Article
- Branching out: the diverse roles of stem and progenitor cells in mammary gland development.Journal of mammary gland biology and neoplasia · 2026Review
- Single-cell mitochondrial lineage tracing: Opportunities and challenges.Quantitative biology (Beijing, China) · 2026Review
- DNA methylation meets lineage tracing: History, recent progress, and future directions.Quantitative biology (Beijing, China) · 2026Article
- Redefining cellular reprogramming with advanced genomic technologies.Nature reviews. Genetics · 2026Review
- Hematopoietic stem cell-independent and -dependent hematopoiesis: new insights and lineage-tracing methods.Experimental hematology · 2026Review
- Modeling mitochondrial inheritance enables high-precision single-cell lineage tracing in humans.bioRxiv : the preprint server for biology · 2026Article
- Blood-based epigenetic instability linked to human aging and disease.Nature communications · 2026Article
- Charting clonal evolution and behavior with GoT-Multi.Cell genomics · 2026Article
- Cell Fate Determination and Lineage Tracing: Technological Evolution and Multidimensional Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
In vivo lineage tracing holds great potential to reveal fundamental principles of tissue development and homeostasis. However, current lineage tracing in humans relies on extremely rare somatic mutations, which has limited temporal resolution and lineage accuracy. Here, we developed a generic lineage-tracing tool based on frequent epimutations on DNA methylation, enabled by our computational method MethylTree. Using single-cell genome-wide DNA methylation datasets with known lineage and phenotypic labels, MethylTree reconstructed lineage histories at nearly 100% accuracy across different cell types, developmental stages, and species. We demonstrated the epimutation-based single-cell multi-omic lineage tracing in mouse and human blood, where MethylTree recapitulated the differentiation hierarchy in hematopoiesis. Applying MethylTree to human embryos, we revealed early fate commitment at the four-cell stage. In native mouse blood, we identified ~250 clones of hematopoietic stem cells. MethylTree opens the door for high-resolution, noninvasive and multi-omic lineage tracing in humans and beyond.
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Registered trials
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