Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver
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Published:2023-11-09
Issue:11
Volume:3
Page:1430-1445
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ISSN:2662-8465
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Container-title:Nature Aging
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language:en
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Short-container-title:Nat Aging
Author:
Nikopoulou ChrysaORCID, Kleinenkuhnen Niklas, Parekh SwatiORCID, Sandoval Tonantzi, Ziegenhain ChristophORCID, Schneider Farina, Giavalisco PatrickORCID, Donahue Kat-Folz, Vesting Anna Juliane, Kirchner MarcelORCID, Bozukova Mihaela, Vossen Christian, Altmüller Janine, Wunderlich ThomasORCID, Sandberg RickardORCID, Kondylis VangelisORCID, Tresch AchimORCID, Tessarz PeterORCID
Abstract
AbstractTissues 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.
Funder
Max-Planck-Gesellschaft Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
Subject
Neuroscience (miscellaneous),Geriatrics and Gerontology,Aging
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