Three-dimensional chromatin re-organization during muscle stem cell aging.
Aging Cell
; 22(4): e13789, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36727578
ABSTRACT
Age-related skeletal muscle atrophy or sarcopenia is a significant societal problem that is becoming amplified as the world's population continues to increase. The regeneration of damaged skeletal muscle is mediated by muscle stem cells, but in old age muscle stem cells become functionally attenuated. The molecular mechanisms that govern muscle stem cell aging encompass changes across multiple regulatory layers and are integrated by the three-dimensional organization of the genome. To quantitatively understand how hierarchical chromatin architecture changes during muscle stem cell aging, we generated 3D chromatin conformation maps (Hi-C) and integrated these datasets with multi-omic (chromatin accessibility and transcriptome) profiles from bulk populations and single cells. We observed that muscle stem cells display static behavior at global scales of chromatin organization during aging and extensive rewiring of local contacts at finer scales that were associated with variations in transcription factor binding and aberrant gene expression. These data provide insights into genome topology as a regulator of molecular function in stem cell aging.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma
/
Senescência Celular
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos