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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: |
Nikopoulou, C.  ORCID: https://orcid.org/0000-0001-7982-7737, Kleinenkuhnen, N., Parekh, S. ORCID: https://orcid.org/0000-0002-4826-1651, Sandoval, T., Ziegenhain, C. ORCID: https://orcid.org/0000-0003-2208-4877, Schneider, F., Giavalisco, P. ORCID: https://orcid.org/0000-0002-4636-1827, Donahue, K.F., Vesting, A.J., Kirchner, M. ORCID: https://orcid.org/0000-0003-0276-0495, Bozukova, M., Vossen, C., Altmüller, J. ORCID: https://orcid.org/0000-0003-4372-1521, Wunderlich, T. ORCID: https://orcid.org/0000-0002-9209-3501, Sandberg, R. ORCID: https://orcid.org/0000-0001-6473-1740, Kondylis, V. ORCID: https://orcid.org/0000-0002-6970-8731, Tresch, A. ORCID: https://orcid.org/0000-0002-4146-6371 and Tessarz, P. ORCID: https://orcid.org/0000-0002-6953-9835
|
| 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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