Fig. 2: P. falciparum iRBC-egress media induces transcriptional downregulation of junctional markers and BBB signaling. | Nature Communications

Fig. 2: P. falciparum iRBC-egress media induces transcriptional downregulation of junctional markers and BBB signaling.

From: Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model

Fig. 2

a Representation of the experimental timeline on 3D-BBB microvessels before and after 24-hour incubation with iRBC-egress media. b–g Single-cell transcriptomic analysis comparing 3D-BBB models exposed to iRBC-egress media and control uRBC media. b UMAP of sequenced cells colored by unsupervised Leiden clustering. c Dot plot of main BBB cell type markers. d UMAP of sequenced cells colored by experimental condition. e Volcano plot of differentially expressed genes in endothelial cells upon 24 h iRBC-egress media incubation, plotting the log2-transformed fold change (log2FC) against the statistical significance (-log10 of the false discovery rate (FDR)). Significantly up- or downregulated genes (FDR < 0.05, log2FC > 0.1 or log2FC < − 0.1, respectively) are marked in red or blue and selected downregulated genes are labeled. f GO-term over-representation analysis on significantly downregulated genes (FDR < 0.05, log2FC < − 0.1) in endothelial cells. Each network node represents one of the most significant GO-terms (adjusted p-value < 0.0001), and edges connect GO-terms with more than 20% gene overlap. GO-term clusters were manually summarized with one label term. P-values were calculated using the hypergeometric distribution (one-sided Fisher’s exact test). Multiple comparisons adjustment was performed using the Benjamini-Hochberg procedure. g Selection of downregulated ligand-receptor interactions important for BBB establishment, identified among the three BBB cell types after exposure to iRBC-egress media using the CellChat package. Arrows point from ligands on sender cells to receptors on receiver cells and are colored by the sender cell. Weights of links are proportional to the interaction strength.

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