Extended Data Fig. 2: LDAM have a unique transcriptional signature that minimally overlaps with published gene expression profiles of microglia in aging and neurodegeneration.

a,b, IPA pathway analysis of genes that are significantly upregulated (a) or downregulated (b) in LD-hi microglia in aging. Analysis based on top 100 down- and up-regulated genes (Fisher’s exact test, Benjamini-Hochberg FDR). c-g, Expression plots comparing RNA-Seq data of LDAM (see Fig. 2) with published RNA-Seq data of microglia in aging (c), AD (d), ALS (e), disease-associated microglia (DAM) (f) and neurodegenerative microglia (MGnD) (g). Data are expressed as signed fdr, i.e the product of log2 FC and log10 fdr. h, Paired dot plot showing FPKM values of LD-lo and LD-hi microglia for ApoE (paired Student’s t-test; P= 0.423). Dotted lines connect LD-lo and LD-hi microglia sorted from the same samples. i, Heatmap showing expression changes of LDAM genes (genes differentially expressed in LD-hi microglia in aging) in LD-hi microglia from GRN^-/- mice, from LPS treated mice, and in microglia clusters revealed by Li et al. (2019) and Hammond et al. (2019)^15,16. Sample size in a,b,h: n = 3 samples per group. Each sample is a pool of microglia from the hippocampi of 3 mice. LD, lipid droplet.