Fig. 2

SOCS3 restores the transcriptional profile of APP astrocytes. a, Hippocampal astrocytes of 9 month-old WT-GFP (N = 7), APP-GFP (N = 4) or APP-SOCS3 (N = 5) mice were isolated by FACS and their transcriptome examined by RNAseq analysis. b, Hierarchical clustering of the ~ 7000 differentially expressed genes between GFP⁺ astrocytes (samples A1-A7) and all other GFP⁻ cells (samples O1-O3), which comprise microglial cells, neurons, oligodendrocyte precursor cells and non-infected astrocytes. c, Socs3 mRNA levels are increased more than 10 times in APP-SOCS3 astrocytes compared to WT-GFP and APP-GFP astrocytes. d, Venn Diagram showing the number of differentially expressed genes between WT-GFP and APP-GFP astrocytes and APP-GFP and APP-SOCS3 astrocytes. e, Expression levels for the 53 genes dysregulated in APP-GFP astrocytes and normalized in APP-SOCS3. Color scale represents mean-centered expression (log2-transformed). Genes belonging to immunity/inflammation pathways are in purple, those belonging to signal transduction are in brown. Genes common to the two pathways are in red. f, Pathway analysis on the 472 genes regulated by SOCS3 in APP astrocytes reveals a specific enrichment in GO terms linked to immunity/ inflammation and signal transduction. Ag. Proc & Pres. = antigen processing and presentation. Cell. = cellular. Ex. = exogenous. Neg. = negative. Pos. = positive. Reg. = regulation. Resp. = response. g, h, SOCS3 normalizes gene expression of cytokines/chemokines (g) and complement factors (h), which are induced in APP-GFP astrocytes. Wald test, * p < 0.05, ** p < 0.01, *** p < 0.001