Comprehensive profiling of lactylation-associated genes in pulmonary hypertension through bulk and single-cell RNA sequencing integration

Figures

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  Fig. 1. Flowchart illustrates the workflow of this study

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  Fig. 2. Identification of Differentially Expressed Genes in Pulmonary Hypertension (PH). A Volcano plot of DEGs in human PH (GSE113439). B Heatmap of gene expression profiles in human PH (GSE113439). C Volcano plot of DEGs in rat PH (GSE186996) D. Heatmap of gene expression profiles in rat PH (GSE186996). E Cross-species analysis of upregulated DEGs in PH. F Cross-species analysis of downregulated DEGs in PH. G GO enrichment analysis of DEGs in PH. H KEGG pathway enrichment analysis of DEGs in PH

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  Fig. 3. LCP1 Drives PH Pathogenesis as a Key Lactylation Target. A GSEA enrichment analysis of lactylation-related genes. B Lactylation signaling ssGSEA score: PH vs Control. C The intersection of PH differential genes and lactylation-related genes. D Verification of LCP1 expression in human and rat PH. E Single-gene GSEA analysis. F GO functional enrichment analysis of LCP1. G Heat maps of differences in 22 immunoinfiltrating cell types. Blue represents low-expression immune cells and red represents high-expression immune cells. H Bubble plot showing the correlation between LCP1 expression and immune cell infiltration

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  Fig. 4. Single-cell RNA sequence analysis. A Lactate content in hPASMCs under hypoxic conditions. B Lactate content in hPASMCs under PDGF-BB stimulation conditions. C Hypoxia induces global and site-specific histone lactylation in hPASMCs. D Verification of mRNA expression of LCP1 in HPH. E Verification of mRNA expression of LCP1 in PAH F. Verification of protein expression of LCP1 in HPH. G Verification of protein expression of LCP1 in PAH. H Cell proliferation assessed by EdU assay. I Apoptpsis assessed by flow cytometry. *p < 0.05 vs normoxia; ** p < 0.01 vs normoxia; # p < 0.05 vs control; ## p < 0.01 vs control

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  Fig. 5. Single-cell RNA sequence analysis. A UMAP classifies cells into 16 distinct clusters. B Differentiation of the control group and PH cell types based on UMAP. C UMAP - based spatial distribution of major cell types in PH samples. D Expression of genes within the lactylation gene set across cells. E The distribution of the scores of the lactylation-related gene set in the single-cell UMAP. F Number and percentage of cells of each cell type between the high and low expression groups of LRGs score. G Comparison of LRG scores of vascular smooth muscle cells between the control group and the PH group

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  Fig. 6. Cell communication. A Cell - cell communication among the specified cell types. B Illustration of the interaction strengths for both incoming and outgoing signals among various cell types. C The incoming and outgoing signaling pathways of each cell type. D The cell-cell interaction network regarding the TWEAK pathway among different cell types. E The cell-cell interaction network related to the TWEAK signaling pathway among different cell types. F TWEAK mediated crosstalk between monocytes/macrophages (TNFSF12) and VSMCs (TNFRSF12A)

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  Fig. 7. Heatmap of correlation between LRGs scores and the HALLMARK pathway in each cell type