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Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells

Author

Listed:
  • Irene Hernando-Herraez

    (Babraham Institute)

  • Brendan Evano

    (Institut Pasteur
    CNRS UMR 3738, Institut Pasteur)

  • Thomas Stubbs

    (Babraham Institute
    Chronomics Limited. Mills & Reeve Llp)

  • Pierre-Henri Commere

    (Institut Pasteur)

  • Marc Bonder

    (Wellcome Genome Campus)

  • Stephen Clark

    (Babraham Institute)

  • Simon Andrews

    (Babraham Institute)

  • Shahragim Tajbakhsh

    (Institut Pasteur
    CNRS UMR 3738, Institut Pasteur)

  • Wolf Reik

    (Babraham Institute)

Abstract

Age-related tissue alterations have been associated with a decline in stem cell number and function. Although increased cell-to-cell variability in transcription or epigenetic marks has been proposed to be a major hallmark of ageing, little is known about the molecular diversity of stem cells during ageing. Here we present a single cell multi-omics study of mouse muscle stem cells, combining single-cell transcriptome and DNA methylome profiling. Aged cells show a global increase of uncoordinated transcriptional heterogeneity biased towards genes regulating cell-niche interactions. We find context-dependent alterations of DNA methylation in aged stem cells. Importantly, promoters with increased methylation heterogeneity are associated with increased transcriptional heterogeneity of the genes they drive. These results indicate that epigenetic drift, by accumulation of stochastic DNA methylation changes in promoters, is associated with the degradation of coherent transcriptional networks during stem cell ageing. Furthermore, our observations also shed light on the mechanisms underlying the DNA methylation clock.

Suggested Citation

  • Irene Hernando-Herraez & Brendan Evano & Thomas Stubbs & Pierre-Henri Commere & Marc Bonder & Stephen Clark & Simon Andrews & Shahragim Tajbakhsh & Wolf Reik, 2019. "Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12293-4
    DOI: 10.1038/s41467-019-12293-4
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    Cited by:

    1. Brendan Evano & Diljeet Gill & Irene Hernando-Herraez & Glenda Comai & Thomas M Stubbs & Pierre-Henri Commere & Wolf Reik & Shahragim Tajbakhsh, 2020. "Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation," PLOS Genetics, Public Library of Science, vol. 16(10), pages 1-21, October.
    2. 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.
    3. Felicia Lazure & Rick Farouni & Korin Sahinyan & Darren M. Blackburn & Aldo Hernández-Corchado & Gabrielle Perron & Tianyuan Lu & Adrien Osakwe & Jiannis Ragoussis & Colin Crist & Theodore J. Perkins , 2023. "Transcriptional reprogramming of skeletal muscle stem cells by the niche environment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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