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Updated: Aug 15, 2025
Micron-scale Resolution Optical Tomography of Entire Mouse Brains with Confocal Light Sheet Microscopy
Published on: October 8, 2013
Molecular and spatial signatures of mouse brain aging at single-cell resolution
William E Allen1, Timothy R Blosser2, Zuri A Sullivan3
1Society of Fellows, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, and Department of Physics, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Abstract:
The diversity and complex organization of cells in the brain have hindered systematic characterization of age-related changes in its cellular and molecular architecture, limiting our ability to understand the mechanisms underlying its functional decline during aging. Here, we generated a high-resolution cell atlas of brain aging within the frontal cortex and striatum using spatially resolved single-cell transcriptomics and quantified changes in gene expression and spatial organization of major cell types in these regions over the mouse lifespan. We observed substantially more pronounced changes in cell state, gene expression, and spatial organization of non-neuronal cells over neurons. Our data revealed molecular and spatial signatures of glial and immune cell activation during aging, particularly enriched in the subcortical white matter, and identified both similarities and notable differences in cell-activation patterns induced by aging and systemic inflammatory challenge. These results provide critical insights into age-related decline and inflammation in the brain.
