Fig. 2

Identification of gene clusters with distinct transcriptional programs in desensitized and primed microglia. a, b Heatmaps with Manhattan distance-based hierarchical clustering analysis of upregulated genes in response to LPS in microglia of C57/BL6 mice three hours after i.p. injection with LPS (LogFC > 1 and FDR < 0.01, PL versus PP). Four main clusters are identified, containing tolerized genes (cluster 2 and 4) and responsive genes (cluster 1 and 3) that show distinct activity to LPS re-stimulation. b Heatmap with Manhattan distance-based hierarchical clustering analysis of all genes differentially expressed between Ercc1^Δ/ko (KO) and Ercc1^wt/ko, Ercc1^wt/Δ, Ercc1^wt/wt (WT) mice with or without LPS injection (n = 3 per experimental condition). Seven clusters are identified, including two clusters of genes primed and trained to LPS treatment in KO mice (cluster 3 and 2). c, d Top 5 GO annotations, based on gene count per GO term, of responsive (cluster 1, 3) and tolerized (cluster 2, 4) gene clusters (c) and the 7 clusters identified in Ercc1^Δ/ko microglia (d).