Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver.
Nat Aging
; 3(11): 1430-1445, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37946043
ABSTRACT
Tissues within an organism and even cell types within a tissue can age with different velocities. However, it is unclear whether cells of one type experience different aging trajectories within a tissue depending on their spatial location. Here, we used spatial transcriptomics in combination with single-cell ATAC-seq and RNA-seq, lipidomics and functional assays to address how cells in the male murine liver are affected by age-related changes in the microenvironment. Integration of the datasets revealed zonation-specific and age-related changes in metabolic states, the epigenome and transcriptome. The epigenome changed in a zonation-dependent manner and functionally, periportal hepatocytes were characterized by decreased mitochondrial fitness, whereas pericentral hepatocytes accumulated large lipid droplets. Together, we provide evidence that changing microenvironments within a tissue exert strong influences on their resident cells that can shape epigenetic, metabolic and phenotypic outputs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcriptoma
/
Epigenoma
Limite:
Animals
Idioma:
En
Revista:
Nat Aging
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha