ArticleNature biotechnology2022
Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues.
Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 65 citations in OpenAlex.
- Differences between mitotically old and young endometrial tumors.The Journal of pathology · 2026Article
- Fluctuating DNA methylation sites encode colorectal tumour growth history.bioRxiv : the preprint server for biology · 2026Article
- Lineage tracing from cellular heritage to disease destiny.Nature genetics · 2026Review
- Conception-calibrated male pediatric tumor mitotic clocks.Communications biology · 2026Article
- Charting single-cell lineages with synthetic and natural barcodes.Nature reviews. Genetics · 2026Review
- PHYFUM: Phylogenetic Reconstruction of Normal and Pre-malignant Tissue Evolution Using Fluctuating Methylation.bioRxiv : the preprint server for biology · 2026Article
- Aggressive Neuroblastomas Start Growing after Infancy.bioRxiv : the preprint server for biology · 2026Article
- DNA methylation meets lineage tracing: History, recent progress, and future directions.Quantitative biology (Beijing, China) · 2026Article
- Modeling the evolutionary dynamics of clonal hematopoiesis.Nature genetics · 2026Review
- Precancerous microenvironment: A signalling perspective.Current opinion in cell biology · 2026Review
- Mapping the temporal landscape of breast cancer using epigenetic entropy.Communications biology · 2025Article
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- Mitochondrial clone tracing within spatially intact human tissues.bioRxiv : the preprint server for biology · 2025Article
- Controlling treatment toxicity in ovarian cancer to prime the patient for tumor extinction therapy.bioRxiv : the preprint server for biology · 2025Article
- Article
- Detecting and quantifying clonal selection in somatic stem cells.Nature genetics · 2025Article
- Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding.Nature communications · 2025Article
- Human brain ancestral barcodes.eLife · 2025Article
- Redefining familial adenomatous polyposis: competition, cooperation, and the path to monoclonality.Familial cancer · 2025Review
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17 authors at 6 institutions in 2 countries.
Funding
Abstract
Molecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated 'flip-flops' between methylated and unmethylated states. We identify endogenous fluctuating CpG (fCpG) sites using standard methylation arrays and develop a mathematical model to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than the colon, with slower stem cell replacement in the small intestine. Germline APC mutation increased the number of replacements per crypt. In blood, we measured rapid expansion of acute leukemia and slower growth of chronic disease. Thus, the patterns of human somatic cell birth and death are measurable with fluctuating methylation clocks (FMCs).
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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 Socratic graph.