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


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


  • Nature Aging


  • Nat Aging 3 (11): 1430-1445


  • 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.