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. 2024 Feb 9;15:1231. doi: 10.1038/s41467-024-45489-4

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Schematic of the human HGF (hHGFtg) and MET (H11^hMET) transgenes, and PB^Cre4 alleles, shown in relation to the mating strategy. b Serum HGF levels of H11^hMET/+:PB^Cre4 (n = 8) and hHGFtg:H11^hMET/+:PB^Cre4 (n = 10) mice. c Representative images of hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining using the indicated antibodies on adjacent prostate tissues from the indicated mice. Scale bars, 400 μm, 20 μm. d Table summarizing the pathological abnormalities in the prostates of H11^hMET/+:PB^Cre4 and hHGFtg:H11^hMET/+:PB^Cre4 mice at the indicated age. e Uniform Manifold Approximation and Projection (UMAP) plots presenting total cells (n = 9236) with highlighting prostatic epithelial cells (both green and red cell clusters) from hHGFtg:H11^hMET/+:PB^Cre4 mice, and epithelial cells (n = 7286) being further sub-clustered, re-clustered, and labeled by epithelial cell cluster (bottom). The dotted line delineated the prostatic epithelial cells. BE basal epithelial cells, LE luminal epithelial cells, UrLE urethral epithelial cells, OE other epithelial cells. f Gene expression UMAP plots for the indicated genes in epithelial cells (n = 7286). Color intensity indicates the scaled expression level. g Heatmap showing DEGs between hMETtg+ and hMETtg− epithelial cells. See Supplementary Data 2. h GSEA plots showing the positive enrichment of the indicated gene sets comparing hMETtg+ and hMETtg− cells. NES normalized enrichment score, FDR false discovery rate. i Violin plots visualizing the expression levels of hMETtg and Wnt downstream target genes in hMETtg+ (n = 4533) and hMETtg− (n = 2753) epithelial cells. Black dots correspond to individual epithelial cells. j Heatmap of pairwise Spearman correlation between the indicated genes in hMETtg+ epithelial cells. Colors reflect the correlation coefficient value. k qPCR analysis of the indicated genes shown as fold change in indicated mouse prostate tissues from four biological replicates. l Representative images of H&E, IHC, and immunofluorescence staining (IF) using indicated antibodies on adjacent sections from hHGFtg:H11^hMET/+:PB^Cre4 mice. Red and blue arrows indicate nuclear β-catenin and co-overlay of pMET with nuclear β-catenin, respectively. Representative images with consistent results from three biological replicates are shown. Scale bars, 12.5 μm. In b and k, data are mean ± s.d. **P < 0.01, ***P < 0.001; Unpaired two-tailed t-tests. See source data and the exact P values in the Source Data file.