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

Nikopoulou, C.; Kleinenkuhnen, N.; Parekh, S.; Sandoval, T.; Ziegenhain, C.; Schneider, F.; Giavalisco, P.; Donahue, K.F.; Vesting, A.J.; Kirchner, M.; Bozukova, M.; Vossen, C.; Altmüller, J.; Wunderlich, T.; Sandberg, R.; Kondylis, V.; Tresch, A.; Tessarz, P.

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., Kleinenkuhnen, N., Parekh, S., Sandoval, T., Ziegenhain, C., Schneider, F., Giavalisco, P., Donahue, K.F., Vesting, A.J., Kirchner, M., Bozukova, M., Vossen, C., Altmüller, J., Wunderlich, T., Sandberg, R., Kondylis, V., 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
ISSN:	2662-8465
Publisher:	Nature Research
Volume:	3
Number:	11
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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