Extended Data Fig. 6: Characterization of main populations in the neurogenic niche with advancing age.
a, UMAP visualization of astrocyte subtypes in (left) Young, (middle) Middle-age and (right) Old mice. b, Spatial distribution of astrocyte subtypes among different ages using tangram cell type mapping. Estimated mapping probability of each astrocyte subtype (color gradient) to DG shown over the H&E images. c, UMAP visualization of astrocyte from Hochgerner 2018 dataset. d, Projection of predicted identities of Astrocyte 1 and Astrocyte 2 in adult astrocytes of Hochgerner 2018 dataset. e, Violin plots showing similar expression of Astrocyte 1- (Igfbp2 and Kcnk1) and 2-specific (Sparc and Nnat) genes in adult astrocytes of Hochgerner et al.34 dataset. f, Pie chart showing the composition of Astrocyte 1 and Astrocyte 2 of adult astrocytes in Hochgerner 2018 dataset (Astrocyte 1: 59.8% and Astrocyte 2: 40.2%). g, UMAP visualization of vascular cell types in (left) Young, (middle) Middle-age and (right) Old mice. h-i, Molecular zonation of vascular compartment. Lower: Smoothened heat map of molecular patterns of the zonation of (h) endothelial and (i) mural cells. Gene expression was ordered based on the peak expression level along the pseudotemporal axis. Color gradient indicates the z-score of gene expression. Upper: Projection of gene expression dynamics of selective genes in pseudotemporal trajectory representing (h) endothelial zonation (Tgfb2, Slc16a1 and Slc38a5) and (i) mural zonation (Myh11, Acta2, Pdgfrb and Kcnj8). Color gradient indicates the log-normalized gene expression level. Shading indicates 95% confidence interval. j, UMAP visualization of microglia subtypes in (left) Young, (middle) Middle-age and (right) Old mice. k, Representative images of proliferating microglia (Microglia 2, indicated by arrowhead) co-stained with Ki67 in DG of (upper) young, (middle) middle-age and (lower) old mice. l, Representative images of inflammation-responding microglia (Microglia 3, indicated by arrowhead) in SGZ of old mice. m-n, Quantification of microglia subpopulations in SGZ at different ages. (m) Quantification of the number of Ki67+ microglia in SGZ (young: 22 ± 4 cells; middle-age: 98 ± 7 cells; old: 36 ± 4 cells; two-tailed unpaired t-test with Welch’s correction, ****P < 0.0001 between young and middle-age, ****P < 0.0001 between middle-age and old, *P = 0.0233 between young and old). (n) Quantification of the number of STAT1+ microglia in SGZ (young: 0 ± 0 cells; middle-age: 8 ± 1 cells; old: 31 ± 3 cells; two-tailed unpaired t-test with Welch’s correction, ***P = 0.0002 between young and middle-age, ***P = 0.0001 between middle-age and old, ****P < 0.0001 between young and old). UMAP, uniform manifold approximation and projection. All data were presented as mean ± SEM. Scale bars, (b) 200 μm and (k and l) 20 μm. H&E, Haematoxylin and eosin.
