Figure 6.
Gene set enrichment analysis of WT and Pf4-Grin1−/− MK transcriptomes. (A) Bar graphs showing differential expression of the gene ontology (GO) biologic processes (i) and Kyoto Encyclopedia of Genes and Genomes pathways (ii) in Pf4-Grin1−/− MKs compared with WT MKs assayed with Clariom S Pico RNA microarray (n = 6 samples per strain). Upregulated pathways are shown in red and downregulated in green. Gene set enrichment analysis was performed using the WebGestalt online tool, and a gene set was considered enriched where the false discovery rate (FDR) adjusted P value was ≤.01. Selected enriched data sets are shown, listed in order of descending FDR. FDR values were transformed and are shown as −log10(FDR). (B-C) Schematics showing transcriptional changes in Pf4-Grin1−/− MKs affecting the phosphatidylinositol signaling system (mmu04070) (B) and inflammatory mediator regulation of transient receptor potential (TRP) channel (mmu04750) (C) pathways mapped with the R package Pathview. Upregulated genes are shown in red and downregulated in green, and genes not mapped from our data set are in gray. Abbreviations of deregulated molecules are provided. Other pathway details can be found through the following links: https://www.genome.jp/dbget-bin/www_bget?mmu04070 (for mmu04070 shown in panel B) and https://www.genome.jp/entry/mmu04750 (for mmu04750 shown in panel C). Molecules marked by numbers refer to a series of inositol, diacylglycerol, or lipid synthases, kinases, and phosphatases. Additional data are provided in supplemental Tables 3 and 4, data supplement, and under Gene Expression Omnibus accession number GSE183044. AC, adenylate cyclase; ASIC, acid-sensing ion channel; BK, kininogen; B1/B2, bradykinin receptors; CaM or CALM, calmodulin; EP, prostaglandin E receptor; GF, insulin-like growth factor; Gq and Gs, guanine nucleotide binding proteins; H1, histamine receptor; 5HTR, serotonin receptor; IL-1β, interleukin-1β; INPP4, inositol polyphosphate-4-phosphatase; p38/JNK, p38 MAP kinase; MKK3/6, MAP kinase kinase 3/6; NGF, nerve growth factor; P2YR, P2Y receptor; P450, cytochrome P450; PAR2, thrombin receptor-like 1; PI4K, phosphatidylinositol 4-kinase; PIK3C, phosphoinositide-3-kinase regulatory subunits; PIKFYVE, phosphoinositide kinase, FYVE type; PKC, protein kinase C; PLCβ, phospholipase Cβ; PP1, protein phosphatase 1; PTEN, phosphatase and tensin homolog; SHIP, inositol polyphosphate-5-phosphatase D; Src, tyrosine-protein kinase Src; TrkA, neurotrophic tyrosine kinase receptor; TRPA1, transient receptor potential cation channel subfamily A member 1; TRPM8, transient receptor potential cation channel subfamily M member 8; TRPV1-TRPV4, transient receptor potential cation channel subfamily V members 1-4.

Gene set enrichment analysis of WT and Pf4-Grin1−/− MK transcriptomes. (A) Bar graphs showing differential expression of the gene ontology (GO) biologic processes (i) and Kyoto Encyclopedia of Genes and Genomes pathways (ii) in Pf4-Grin1−/− MKs compared with WT MKs assayed with Clariom S Pico RNA microarray (n = 6 samples per strain). Upregulated pathways are shown in red and downregulated in green. Gene set enrichment analysis was performed using the WebGestalt online tool, and a gene set was considered enriched where the false discovery rate (FDR) adjusted P value was ≤.01. Selected enriched data sets are shown, listed in order of descending FDR. FDR values were transformed and are shown as −log10(FDR). (B-C) Schematics showing transcriptional changes in Pf4-Grin1−/− MKs affecting the phosphatidylinositol signaling system (mmu04070) (B) and inflammatory mediator regulation of transient receptor potential (TRP) channel (mmu04750) (C) pathways mapped with the R package Pathview. Upregulated genes are shown in red and downregulated in green, and genes not mapped from our data set are in gray. Abbreviations of deregulated molecules are provided. Other pathway details can be found through the following links: https://www.genome.jp/dbget-bin/www_bget?mmu04070 (for mmu04070 shown in panel B) and https://www.genome.jp/entry/mmu04750 (for mmu04750 shown in panel C). Molecules marked by numbers refer to a series of inositol, diacylglycerol, or lipid synthases, kinases, and phosphatases. Additional data are provided in supplemental Tables 3 and 4, data supplement, and under Gene Expression Omnibus accession number GSE183044. AC, adenylate cyclase; ASIC, acid-sensing ion channel; BK, kininogen; B1/B2, bradykinin receptors; CaM or CALM, calmodulin; EP, prostaglandin E receptor; GF, insulin-like growth factor; Gq and Gs, guanine nucleotide binding proteins; H1, histamine receptor; 5HTR, serotonin receptor; IL-1β, interleukin-1β; INPP4, inositol polyphosphate-4-phosphatase; p38/JNK, p38 MAP kinase; MKK3/6, MAP kinase kinase 3/6; NGF, nerve growth factor; P2YR, P2Y receptor; P450, cytochrome P450; PAR2, thrombin receptor-like 1; PI4K, phosphatidylinositol 4-kinase; PIK3C, phosphoinositide-3-kinase regulatory subunits; PIKFYVE, phosphoinositide kinase, FYVE type; PKC, protein kinase C; PLCβ, phospholipase Cβ; PP1, protein phosphatase 1; PTEN, phosphatase and tensin homolog; SHIP, inositol polyphosphate-5-phosphatase D; Src, tyrosine-protein kinase Src; TrkA, neurotrophic tyrosine kinase receptor; TRPA1, transient receptor potential cation channel subfamily A member 1; TRPM8, transient receptor potential cation channel subfamily M member 8; TRPV1-TRPV4, transient receptor potential cation channel subfamily V members 1-4.

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