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scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood

Author

Listed:
  • Marc Jan Bonder

    (German Cancer Research Center
    European Molecular Biology Laboratory
    University of Groningen, University Medical Center Groningen
    Oncode Institute)

  • Stephen J. Clark

    (Cambridge Institute of Science
    The Babraham Institute)

  • Felix Krueger

    (Cambridge Institute of Science
    The Babraham Institute)

  • Siyuan Luo

    (ETH Zurich)

  • João Agostinho de Sousa

    (ETH Zurich)

  • Aida M. Hashtroud

    (Max Planck Institute for the Physics of Complex Systems
    Ludwig-Maximilians-Universität)

  • Thomas M. Stubbs

    (The Babraham Institute
    Chronomics Limited)

  • Anne-Katrien Stark

    (The Babraham Institute)

  • Steffen Rulands

    (Max Planck Institute for the Physics of Complex Systems
    Ludwig-Maximilians-Universität)

  • Oliver Stegle

    (German Cancer Research Center
    European Molecular Biology Laboratory)

  • Wolf Reik

    (Cambridge Institute of Science
    The Babraham Institute
    Hinxton)

  • Ferdinand von Meyenn

    (ETH Zurich
    King’s College London)

Abstract

Ageing is the accumulation of changes and decline of function of organisms over time. The concept and biomarkers of biological age have been established, notably DNA methylation-based clocks. The emergence of single-cell DNA methylation profiling methods opens the possibility of studying the biological age of individual cells. Here, we generate a large single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. The number of genes expressed increases with age, but gene-specific changes are small. We next develop scEpiAge, a single-cell DNA methylation age predictor, which can accurately predict age in (very sparse) publicly available datasets, and also in single cells. DNA methylation age distribution is wider than technically expected, indicating epigenetic age heterogeneity and functional differences. Our work provides a foundation for single-cell and sparse data epigenetic age predictors, validates their functionality and highlights epigenetic heterogeneity during ageing.

Suggested Citation

  • Marc Jan Bonder & Stephen J. Clark & Felix Krueger & Siyuan Luo & João Agostinho de Sousa & Aida M. Hashtroud & Thomas M. Stubbs & Anne-Katrien Stark & Steffen Rulands & Oliver Stegle & Wolf Reik & Fe, 2024. "scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51833-5
    DOI: 10.1038/s41467-024-51833-5
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    References listed on IDEAS

    as
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