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Modeling mitochondrial inheritance enables high-precision single-cell lineage tracing in humans - PubMed

4 hours ago
  • #lineage tracing
  • #mitochondrial DNA
  • #single-cell analysis
  • MitoDrift is a probabilistic framework for high-precision lineage tracing using mitochondrial DNA (mtDNA) mutations.
  • It integrates Wright-Fisher drift dynamics with sparse single-cell measurements to refine lineage trees.
  • Validation shows MitoDrift outperforms existing methods in precision and clonal recovery.
  • Applied to human hematopoiesis, it reveals age-associated decline in clonal diversity and heritable regulatory programs.
  • In multiple myeloma, MitoDrift detects therapy-associated clonal remodeling and links gene regulatory programs to drug sensitivity.
  • Enables quantitative lineage-state analysis in human tissues, connecting clonal history to transcriptional and epigenetic programs.