Fig. 6: Molecular features of myeloid-derived cells in hyperactivated YAP1-induced renal carcinogenesis.
From: Targeting the disrupted Hippo signaling to prevent neoplastic renal epithelial cell immune evasion
A, B Heatmap demonstrates significantly altered genes in myeloid cells in renal tissues of Pax8-rtTA;Tet-on-YAPS127A mice induced with doxycycline for seven days (D7, A) or four months (M4, B). Myeloid cells in renal tissues of non-induced mice were used as control (CTR). Significant genes involved in renal tissue microenvironment reprogramming are listed on the left side of the heatmap. C, D Gene set ontology enrichment analysis showing significantly altered signaling pathways in myeloid cells in renal tissues of Pax8-rtTA;Tet-on-YAPS127A mice induced with doxycycline for seven days (D7, C) or four months (M4, D). Myeloid cells in renal tissues of non-induced mice were used as control (CTR). Representative pathways involved in renal tissue microenvironment reprogramming are listed in the plots. 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. E UMAP projection of eight clusters identified in the myeloid cells (clusters are labeled in UMAP). F Violin plots of representative marker genes across identified myeloid cell clusters. G UMAP plots showing changes in myeloid cell subpopulations in renal tissues of Pax8-rtTA;Tet-on-YAPS127A mice induced with doxycycline for seven days (D7) and four months (M4). Renal tissues from non-induced mice were used as a control (CTR). Please note the drastic accumulation of myeloid-derived suppressor cells (MDSCs) in the renal tissue of Pax8-YAPS127A mice. H Dynamic change of myeloid cell subpopulations in renal tissue of PAX8-rtTA;Tet-on-YAPS127A mice induced with doxycycline for seven days (D7) and four months (M4). Renal tissues from non-induced mice were used as a control (CTR). *: significantly different when compared to CTR. Statistical difference were performed with scCODA with FDR = 0.05. Please note that the vast majority of increased myeloid cells are MDSCs. I) UMAP plots showing high expression of key genes associated with MDSC functionality in renal tissues of Pax8-YAPS127A mice induced with doxycycline for seven days (D7) and four months (M4). Renal tissues from non-induced mice were used as a control (CTR). 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.
