Many are called but few are chosen – from multiple clonal origins to one winner

Life Medicine, Год журнала: 2025, Номер 4(1)

Опубликована: Фев. 1, 2025

Язык: Английский

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BASELINE: A CRISPR Base Editing Platform for Mammalian-Scale Single-Cell Lineage Tracing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

A cell's fate is shaped by its inherited state, or lineage, and the ever-shifting context of environment. CRISPR-based recording technologies are a promising solution to map lineage developing system, yet challenges remain regarding single-cell recovery, engineering complexity, scale. Here, we introduce BASELINE, which uses base editing generate high-resolution trees in conjunction with profiling. BASELINE Cas12a adenine editor irreversibly edit nucleotides within 50 synthetic target sites, integrated multiple times into genome. We show that accumulates lineage-specific marks over wide range biologically relevant intervals, more than 4300 bits information model pancreatic cancer, 50X increase existing technologies. Single-cell sequencing reveals high-fidelity capture these recorders, recovering reconstructions up 40 cell divisions deep, estimated mammalian development. expect apply lineage-tracing projects development disease, especially cellular makes small, distributed systems challenging.

Язык: Английский

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Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells

Genome biology, Год журнала: 2025, Номер 26(1)

Опубликована: Март 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.

Язык: Английский

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Single-cell phylodynamic inference of stem cell differentiation and tumor evolution

Cell Systems, Год журнала: 2025, Номер unknown, С. 101244 - 101244

Опубликована: Апрель 1, 2025

Язык: Английский

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Ultra-precise 3D maps of cancer cells unlock secrets of how tumours grow

Nature, Год журнала: 2024, Номер unknown

Опубликована: Окт. 30, 2024

Язык: Английский

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