Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells

Figure 3

Differential chromatin accessibility and gene expression in memory versus naïve CD4 T cells as well as in GM-CSF-positive versus negative cells. (a, b) ATAC-seq data were CQN normalized and differential accessibility between the indicated cell population comparisons was calculated ((a) memory vs. naïve CD4 T cells; (b) GM-CSF-positive vs. negative CD4 T cells). Volcano plots show each consensus peak as a single dot, and lines indicate the threshold for calling a DAR ( and >25% fold change); DARs are depicted in black. (c, d) Differential gene expression was calculated from RNA-seq data for cell population comparisons as in (a, b). Lines indicate the threshold for calling a DEG ( and >25% fold change); DEGs are depicted in black. (e) A selection of DARs in memory vs. naïve was studied for being assigned to genes known to play a role in T cell memory. (fold change (memory/naïve)) for selected DARs are plotted, and colors indicate the category that the respective region is assigned to (TSS: transcription start site; TTS: transcription termination site). (f) Known T cell memory “up” (black) or T cell memory “down” (grey) genes based on previous literature were selected if differentially expressed (DEG in memory vs. naïve) in the present data. (fold change (memory/naïve)) for these selected DEGs is plotted; represent upregulation and represent downregulation in memory T cells. Colors indicate whether the gene was previously described to be “up” or “down” in memory T cells. (g) Gene set enrichment analysis (GSEA) using gene sets from published transcriptome data featuring naïve and memory T cell subsets (GSE accession numbers as displayed) and a ranked gene list of our memory versus naïve T cell data. Ranking was based on (fold change (memory/naïve))). Gene sets containing both human naïve and memory T cell data were retrieved from the MSigDB database [48]. NES: normalized enrichment score; pval: value; padj: FDR.