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High-resolution, noninvasive single-cell lineage tracing in mice and humans based on DNA methylation epimutations [LK_RNAseq; transcriptome of single cells]

GSE262219 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/11/16 Platform GPL24247
Summary
In vivo lineage tracing holds great potential to reveal fundamental principles of tissue development and homeostasis. However, lineage tracing in humans relies on DNA mutations that are extremely rare. In mice, the improved genetic labeling approach has low resolution over cell division histories. Here, we demonstrated for the first time that frequent epimutations on DNA methylation can be exploited to infer lineage histories in normal cells, enabled by our newly developed computational method MethyTree. Using both in-house and public sparse single-cell DNA methylation datasets with known lineage labels, MethyTree reconstructed lineage histories at high resolution and accuracy across different cell types, stages, and species. Applying MethyTree, we identified the first fate decision in human embryo development and pinpointed in total ~230 clones of hematopoietic stem cells in mice. Our study opens the door for high-resolution, noninvasive lineage tracing in mice, humans and beyond.
Published in
High-resolution, noninvasive single-cell lineage tracing in mice and humans based on DNA methylation epimutations
Chen M, Fu R, Chen Y et al. · Nature methods 2025 · PMID 39820752 · doi:10.1038/s41592-024-02567-1
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Also filed as BioProject PRJNA1090838 and SRA study SRP497175. Searching any of these in the dataset finder brings you back here.

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