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Fig. 6 | Genome Medicine

Fig. 6

From: Single-cell multimodal analysis identifies common regulatory programs in synovial fibroblasts of rheumatoid arthritis patients and modeled TNF-driven arthritis

Fig. 6

Inference of SF trajectories in the arthritic joint by RNA velocity analysis. A RNA velocity analysis recapitulating cell transitions and dynamic relations between SF clusters in the hTNFtg samples. Large panel: the UMAP highlights the existence of a pathogenic branch comprising S2d - S4b - S4a. Small panel: RNA velocity analysis in WT and hTNFtg samples. B Overlap of differentially expressed genes with scVelo driver genes, indicates genes potentially related to disease progression. In the first heatmap (left), avgLogFC values for DE genes, as calculated from inter-cluster and intra-cluster comparisons in each sample, are shown. In the second heatmap, binary values signify upregulation (orange) or downregulation (purple) of those genes in the hTNFtg vs WT comparison. In the third heatmap (right), genes are ranked according to the likelihood to drive the underlying cellular process. In the fourth heatmap (center), the scaled expression of the 107 overlapping genes is plotted. Cells are ordered by latent time values, after an S2b cell was set as the root of the trajectory. The gene expression patterns reveal a transcriptional gradient along the latent time axis in the hTNFtg SFs. C scATAC-seq semi-supervised trajectory analysis supports the existence of the aforementioned pathogenic branch. The color indicates the cellular fate across the inferred trajectory. D Heatmap showing the integrated gene expression activity (left panel) and the TF motif deviation (right panel) of positive TF regulators along the pseudotemporal ordered cells in the S2b- S2a - S2d - S4b - S4a branch. TFs gene expression is significantly correlated with TF motif deviation across the cell trajectory. E Binary heatmap of disease-related TFs and genes epigenetically primed for disease activation. Purple denotes that the TF regulates the gene, while white denotes a lack of regulation. The barplot summarizes the percentage of genes regulated by each TF

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