Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells.
Nat Commun
; 10(1): 4361, 2019 09 25.
Article
en En
| MEDLINE
| ID: mdl-31554804
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células Madre
/
Envejecimiento
/
Senescencia Celular
/
Metilación de ADN
/
Transcriptoma
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article