Extended Data Fig. 8: Single-cell gene expression and chromatin accessibility of CEBEP/β target genes in combo-treated RMs.
From: TGF-β mediates epigenetic control of innate antiviral responses and SIV reservoir size
A. UMAP plot showing the downregulated (blue) expression of genes from the TNF pathway in T cells from CA-vDNAlo RMs. B. UMAP plot showing the downregulated (blue) expression of genes from the TNF pathway in myeloid cells and FDCs from CA-vDNAlo RMs. C. Expression of effector genes IFNG, GZMB, PRF1, TBX21, CD69, CD40LG and TNFRSF9 in T cells. The lighter regions in the density plots indicate higher density of cells expressing the selected genes. The dot plot shows the frequencies of different subsets expressing these markers and its average expression (red to blue: high to low expression). D. GSEA was used to identify effector pathways (MSigDB, Hallmark) that significantly (P ≤ 0.05) differentiated CA-vDNAhi (left) and CA-vDNAlo (right) from control RMs in LNMCs pre-ATI. Heatmap illustrates NES for pathways of the effector modules, the NES scale ranges from low (blue) to high (red). Columns represent relative enrichment in CA-vDNAhi (left) and CA-vDNAlo RMs (right), whereas rows represent pathways. n = 10 combo-treated RMs (6 CA-vDNAhi and 4 CA-vDNAlo). GSEA is a statistical method to determine whether members of a particular gene set preferentially occur toward the top or bottom of a ranked-ordered gene list where genes are ranked by the strength of their association with the outcome of interest. More specifically, GSEA calculates an enrichment score (NES) that reflects the degree to which a set of genes is overrepresented among genes differentially expressed. E. Network inference (Cytoscape) was used to plot the significant effector LEGs (P < 0.05) of the pathways in E that were significantly inversely correlated with CA-vRNA (blue diamond) 24 weeks post-ATI in LNMCs of combo-treated RMs. Connecting lines highlight gene-gene interactions. Line thickness represents the strength of gene interactions. CA-vDNA: cell-associated viral DNA; LEG: leading-edge genes; LNMCs: lymph node mononuclear cells; NES: normalized enrichment scores; RMs: rhesus macaques; UMAP: uniform manifold approximation and projection.
