Fig. 6: YAP-TEAD inhibition by verteporfin reduces profibrotic genes in human fibrotic lung tissue ex vivo. | Nature Communications

Fig. 6: YAP-TEAD inhibition by verteporfin reduces profibrotic genes in human fibrotic lung tissue ex vivo.

From: Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models

Fig. 6

A Uniform Manifold Approximation and Projection (UMAP) representation of 11753 epithelial nuclei from 24 PCLS generated from 2 control donor lungs (4 PCLS per subject and per condition); the UMAPs are labeled by condition (4 PCLS per subject and per condition): Vehicle (Veh), Fibrotic Cocktail (FC)+Veh, FC+Verteporfin (VP), (top panel) or by cell type, Aberrant Basaloid Like 1 and 2; alveolar type 1 (AT1) cell; alveolar type 2 (AT2) cell, Basal cell; and Inflammatory Basal Cells (BCs)(bottom panel). B Heat map of normalized gene expression per cell type within each condition; Columns are ordered by disease status and cell type. C Differential gene expression between the two aberrant basaloid nuclei clusters, genes labeled in red are upregulated in aberrant basaloid like 1 cluster (log2FoldChange > 0.5; adjusted p-value < 0.05, Bonferroni correction in FindMarkers()); labeled genes are selected based on GO enrichment in (D). D Gene Ontology enrichment based on the upregulated genes in aberrant basaloid Like 1 cells in comparison to aberrant basaloid like 2 cells; the top 4 terms in the cell compartments (CC) terms are displayed. E Percent makeup distributions of each identified cell type across all sampled epithelial cells per subject within each condition. Each dot represents a single subject. Adj.p-value calculated in REACTOME with Benjamini–Hochberg. F Violin plots of expression of aberrant basaloid cell markers and Lysyl oxidase (LOX) family genes. G Differential gene expression of PCLS treated with fibrotic cocktail and verteporfin compared with fibrotic cocktail alone in the aberrant basaloid like 1 cluster (adjusted p-value  <  0.05, Bonferroni correction in FindMarkers()), negative fold change > −0.5 (blue) ie Downregulated, and positive fold change >0.5 (red) ie Upregulated. H Feature-plots of LOX genes showing gene expression across all nuclei in all samples. Source data for Fig. 6 are provided at https://doi.org/10.5281/zenodo.14229565.

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