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Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver

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Item Type:Article
Title:Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver
Creators Name:Nikopoulou, C. and Kleinenkuhnen, N. and Parekh, S. and Sandoval, T. and Ziegenhain, C. and Schneider, F. and Giavalisco, P. and Donahue, K.F. and Vesting, A.J. and Kirchner, M. and Bozukova, M. and Vossen, C. and Altmüller, J. and Wunderlich, T. and Sandberg, R. and Kondylis, V. and Tresch, A. and Tessarz, P.
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.
Keywords:Epigenome, Hepatocytes, Liver, Metabolome, Transcriptome / Genetics, Animals, Mice
Source:Nature Aging
Publisher:Nature Research
Page Range:1430-1445
Date:November 2023
Official Publication:https://doi.org/10.1038/s43587-023-00513-y
PubMed:View item in PubMed

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