Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
08
05
2023
accepted:
27
09
2023
medline:
16
11
2023
pubmed:
10
11
2023
entrez:
9
11
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37946043
doi: 10.1038/s43587-023-00513-y
pii: 10.1038/s43587-023-00513-y
pmc: PMC10645594
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1430-1445Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC 2030 - 390661388
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 415274764
Informations de copyright
© 2023. The Author(s).
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