Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells DOI Creative Commons
Xin Wang, Kun Wang, Weixing Zhang

et al.

Genome biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 26, 2025

Mitochondrial DNA (mtDNA) variants hold promise as endogenous barcodes for tracking human cell lineages, but their efficacy reliable lineage markers are hindered by the complex dynamics of mtDNA in somatic tissues. Here, we use computational modeling and single-cell genomics to thoroughly interrogate origin clonal across various biological settings. Our findings reveal that majority which specifically present a subpopulation, termed subpopulation-specific variants, pre-existing heteroplasmies first instead de novo mutations during divisions. Moreover, demonstrate limited discriminatory power among different genuine lineages under weak expansion; however, certain with consistently high frequencies subpopulation capable faithfully labeling scenarios stringent expansion, such strongly expanded T populations diseased conditions hematopoiesis aged individuals. Inspired our simulations, introduce informative score, facilitating identification mitochondrial tracing modalities genomic data. Combining sequencing, study reveals performance is highly dependent on extent thus should be considered when applying tracing.

Language: Английский

Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells DOI Creative Commons
Xin Wang, Kun Wang, Weixing Zhang

et al.

Genome biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 26, 2025

Mitochondrial DNA (mtDNA) variants hold promise as endogenous barcodes for tracking human cell lineages, but their efficacy reliable lineage markers are hindered by the complex dynamics of mtDNA in somatic tissues. Here, we use computational modeling and single-cell genomics to thoroughly interrogate origin clonal across various biological settings. Our findings reveal that majority which specifically present a subpopulation, termed subpopulation-specific variants, pre-existing heteroplasmies first instead de novo mutations during divisions. Moreover, demonstrate limited discriminatory power among different genuine lineages under weak expansion; however, certain with consistently high frequencies subpopulation capable faithfully labeling scenarios stringent expansion, such strongly expanded T populations diseased conditions hematopoiesis aged individuals. Inspired our simulations, introduce informative score, facilitating identification mitochondrial tracing modalities genomic data. Combining sequencing, study reveals performance is highly dependent on extent thus should be considered when applying tracing.

Language: Английский

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