Figure 4.

The pro-inflammatory response caused by ATP preconditioning is observed at the transcriptional level

(A) Volcano plots depicting the differential expression between +ATP and Naive, and between +ATP+LPS and +LPS microglia-like cells. Differentially expressed genes (DEGs) are considered for adjusted p value (FDR) < 0.05. Upregulated DEGs (log2(fold change) > 0) are highlighted in red, and downregulated DEGs (log2(fold change) < 0) in green.

(B) Venn diagram of the overlap between the list of genes up and downregulated in the two comparisons.

(C) Heatmap representation of the DEGss obtained for the pairwise comparison between all microglia-like conditions. Gene expression is represented as the Z score of the normalized counts. The significance cutoff was of adjusted p value (FDR) < 0.05. Unsupervised clustering divided the DEGs in twelve modules (E1-E12). DEGs associated with differentially methylated positions (DMPs) are highlighted (black lines).

(D) Violin plot representation of the mean Z score of the normalized counts of each DEG module in monocytes and in all microglia-like cell groups.

(E) Selected list of significantly enriched gene ontology (GO) terms for each of modules of DEGs. The significance of enrichment is represented by the negative of the log of the adjusted p value, the enrichment fold change and the number of gene hits.

(F) Transcription factor (TF) enrichment of all significant TF (adjusted p value (FDR) < 0.05) in both differential expression comparisons (+ATP vs. Naive and +ATP+LPS vs. +LPS). Significance is represented by the NES (Normalized Enrichment Score) and the negative of log of the adjusted p value (FDR). See also Figure S3 and Tables S5 and S6.