Fig. 3 |. Diverse cell states of glial and endothelial cells in the aging DLPFC.

a,d,h, Diversity of non-neuronal cell states in the aging DLPFC. UMAP embedding of microglia with 2,837 nuclei (a), astrocytes with 29,486 nuclei (d) and endothelia with 2,296 nuclei (h), colored by clusters capturing distinct cell states. b,e, Dot plots of the z-scored mean expression level in expressing nuclei (color) and percentage of expressing nuclei (circle size) of selected marker genes (columns) across microglial (b) or astrocyte (e) subsets (rows). c,f,i, Enriched pathways (hypergeometric test, FDR-adjusted p-value < 0.05, blue color) in up-regulated gene signatures for each subset of microglial (c), astrocyte (f) or endothelial (i) nuclei (columns). g, Spatial transcriptomics using the Visium platform showing the position of Ast.3 cells by marker gene ID3 and reactive astrocytes marker GFAP. Oligodendrocyte marker MBP marks the white matter border. Bottom right, schematic annotation of the tissue. Additional tissues and genes are shown in Extended Data Fig. 5. j, Continuum of expression programs in oligodendrocyte cells inferred by topic modeling^19–22. For each topic model panel: UMAP embedding of oligodendrocyte cells, colored by the weight of each topic per cell (right); the top scoring genes (colored by the score), computed as the Kullback–Leibler (KL) divergence between the expression level and the topic’s weight across cells (red color scale, left); and the cumulative distribution function of topic weights for cells split by the sample of origin to four major archetypes of the aging population (as in Fig. 2d).