Fig. 9

Identification and validation of PTPN11 (SHP-2) as a novel target to reverse chronic neuroinflammation. A Venn diagram of significant DEGs that were associated with the GO term(s) of “Molecular Function: Binding” and “Cell Compartment: Integral Part of Plasma Membrane”. 1,173 genes identified by this analysis were then analyzed via GSEA for Kegg pathways. Significant pathways and associated adjusted p-values indicated in histogram. B Heat map of differential gene expression of phagocytosis receptor genes, grouped by whether the protein encoded by the gene signals via ITAM, ITIM, or ITSM. Inset indicates differential expression of genes for signaling molecules associated with ITAM and ITIM receptors. C Analysis of genes that exhibit cell type-specific expression indicates increases in neuron-associated transcription and decreases in microglial and astrocyte transcription in response to inhibitors of PTPN11. D Heat maps of gene panels for specific domains of biology indicate suppression of disease-associated microglia genes, astrocyte activation genes, and genes associated with inflammatory processes. Genes associated with neurotransmitter receptors were increased