Cited by 245Epigenetics and DNA MethylationSingle-cell and spatial transcriptomicsGenomics and Chromatin Dynamics

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

Open access
Hernando-Herraez, Irene, Evano, Brendan, Stubbs, Thomas, Commere, Pierre-Henri, Jan Bonder, Marc, Clark, Stephen, Andrews, Simon, Tajbakhsh, Shahragim +1 more·2019·Nature Communications

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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.

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  • In muscle, single-cell multi-omic studies reveal that ageing is accompanied by transcriptional heterogeneity, especially in genes that impact stem cell-niche interactions.

    “In muscle, single-cell multi-omic studies reveal that ageing is accompanied by transcriptional heterogeneity, especially in genes that impact stem cell–niche interactions67.”
  • In muscle, DNA methylation changes with ageing in MuSCs, with increased heterogeneity (accompanied by transcriptional heterogeneity), suggesting an epigenetic drift with ageing.

    “In muscle, DNA methylation changes with ageing in MuSCs, with increased heterogeneity (accompanied by transcriptional heterogeneity), suggesting an epigenetic drift with ageing33,67.”

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Authors
Hernando-Herraez, I., Evano, B., Stubbs, T., Commere, P.-H., Jan Bonder, M., Clark, S., Andrews, S., Tajbakhsh, S., & Reik, W.
Affiliations
  • Babraham Institute (GB)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Hernando-Herraez, Irene
  • Tajbakhsh, Shahragim
  • Reik, Wolf
Venue
Nature Communications
Published
2019-09-25
Volume
10
Issue
1
Pages
4361-4361
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2976009347
Cited by
236
References
45
Citations by year
2026: 31 · 2025: 25 · 2024: 35 · 2023: 40 · 2022: 37 · 2021: 29 · 2020: 33 · 2019: 5 · 2016: 1
FWCI
8.97
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Agence Nationale de la Recherche (ANR-10-LABX-73)
  • Association Française contre les Myopathies (332893)
  • RCUK | Biotechnology and Biological Sciences Research Council (CBBS/E/B/000C0425)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
aging, muscle stem cells, epigenetic drift, transcriptional heterogeneity, cell-to-cell variability, single-cell multi-omics, promoter methylation, DNA methylation clocks, transcriptional regulatory networks, stem cell heterogeneity
MeSH terms
Aging, Animals, Cells, Cultured, Humans, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Muscles, Promoter Regions, Genetic, Stem Cells, Cellular Senescence, DNA Methylation, Gene Expression Profiling, Epigenesis, Genetic, Epigenomics, Single-Cell Analysis, Transcriptome, Gene Ontology

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