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

Autor: Bonder MJ; Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany. bonder.m.j@gmail.com.; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. bonder.m.j@gmail.com.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. bonder.m.j@gmail.com.; Oncode Institute, Utrecht, The Netherlands. bonder.m.j@gmail.com., Clark SJ; Altos Labs, Cambridge Institute of Science, Cambridge, UK. sclark@altoslabs.com.; Epigenetics Programme, The Babraham Institute, Cambridge, UK. sclark@altoslabs.com., Krueger F; Altos Labs, Cambridge Institute of Science, Cambridge, UK.; Bioinformatics Group, The Babraham Institute, Cambridge, UK., Luo S; Laboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Agostinho de Sousa J; Laboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Hashtroud AM; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.; Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-Universität, Munich, Germany., Stubbs TM; Epigenetics Programme, The Babraham Institute, Cambridge, UK.; Chronomics Limited, London, UK., Stark AK; Immunology Programme, The Babraham Institute, Cambridge, UK., Rulands S; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.; Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-Universität, Munich, Germany., Stegle O; Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany.; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Reik W; Altos Labs, Cambridge Institute of Science, Cambridge, UK. wreik@altoslabs.com.; Epigenetics Programme, The Babraham Institute, Cambridge, UK. wreik@altoslabs.com.; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. wreik@altoslabs.com., von Meyenn F; Laboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. ferdinand.vonmeyenn@hest.ethz.ch.; Department of Medical and Molecular Genetics, King's College London, London, UK. ferdinand.vonmeyenn@hest.ethz.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 31; Vol. 15 (1), pp. 7567. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1038/s41467-024-51833-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE