Fig. 5: Molecular features of transformed renal epithelial cells.
From: Targeting the disrupted Hippo signaling to prevent neoplastic renal epithelial cell immune evasion
A UMAP plots showing the expression of YAP1 in different types of cells in the renal tissues. Please note that YAP1 is primarily expressed in epithelial cells. B GSEA analyzes showing the enrichment of genes associated with YAP1 conserved signature in renal epithelial cells induced with Dox for seven days (D7) or four months (M4). C UMAP plots showing the changes of epithelial cell subpopulations in control (CTR) and YAPS127A-induced (for 7 days and 4 months) renal tissues. Please note that the numbers of cells in cluster 5 (C5) and cluster 11 (C11) are significantly increased after doxycycline induction of transgene expression. D GSEA analyzes showing the enrichment of genes associated with YAP1 conserved signature in C5 and C11 subpopulations after inducing transgene expression with doxycycline for 7 days (D7) or 4 months (M4). E Heatmap demonstrates significantly altered genes in the C5 cluster of proximal tubal epithelial cells after inducing transgene with doxycycline for 7 days (D7) or 4 months (M4). Renal epithelial cells from the non-induced mice were used as control (CTR). The significantly altered genes involved in extracellular matrix reprogramming are listed on the left side of the heatmap. F Gene ontology enrichment analysis showing alteration of signaling pathways involved in the transformation of cluster 5 (C5) cells in D7 early lesions and M4 pRCC tumor tissues. P.adjust is Benjamini-Hochberg adjusted p values. And P values were derived from GSEA permutation based on an adaptive multi-level split Monte-Carlo scheme implemented in fgsea R package. G Heatmap demonstrates significantly altered genes in the C11 cluster of proximal tubal epithelial cells after inducing transgene with doxycycline for 7 days (D7) or 4 months (M4). Renal epithelial cells from the non-induced mice were used as control (CTR). The significantly altered genes involved in extracellular matrix reprogramming are listed on the left side of the heatmap. H Gene ontology enrichment analysis showing alteration of signaling pathways involved in the transformation of cluster 11 (C11) cells in D7 early lesions and M4 pRCC tumor tissues. P.adjust is Benjamini-Hochberg adjusted p values. And P values were derived from GSEA permutation based on an adaptive multi-level split Monte-Carlo scheme implemented in fgsea R package. I Heatmap showing expression of genes encoding for chemokines, cytokines, and growth factors that are associated with MDSC accumulation and immune suppression in C5 and C11 epithelial cells. Please note that mice in the M4 group were generated using a low dose/chronic induction protocol in order to avoid acute neoplasia-associated kidney failure.
