Fig. 7

Fig. 7

A Modeling loss of mesothelial homeostasis during mesothelioma tumorigenesis: 6–8 weeks-old Nf2+/− C57Bl/6J mice exposed to crocidolite intra-peritoneally (400 µg) every 3 weeks with eight total treatments, parallel to controls. 33 weeks after initial exposure, tissue was collected. B Heatmap of LPM-associated genes, either upregulated (Msln, Wt1) or downregulated (Nf2, Bap1) mesothelioma genes, and negative control (Tubb4a). Bins colored by row-scaled log2-normalized counts; columns (samples) split by treatment group; rows and columns ordered by hierarchical clustering (scaled expression values). Right side row indicates raw count range. C Immunoreactivity of Hand2 protein in mouse mesothelioma. D Relative expression of HAND2 by qPCR in normal pleura (n = 4) and human malignant mesothelioma (n = 36); trend (p = 0.0596) towards increased HAND2 levels in tumors (Mann–Whitney two-tailed test, exact p-value). Mean ± SE. E Immunoreactivity of HAND2 protein in HAND2-high human mesothelioma. F Heatmap representing unsupervised hierarchical clustering of human mesothelioma from TCGA RNA-seq (n = 87), depicting expression of mesothelial progenitor-associated LPM genes, mesothelioma-associated genes (WT1, MSLN, BAP1, NF2, and TP53), unrelated control (YY1, OTX2, and BRCA1) and housekeeping genes (ATP5PB, GUSB, TBP, and GAPDH). Columns represent histotypes, rows represent log10-transformed, batch-normalized mRNA expression levels of mesothelioma samples. Scale bars C 50 µm, and D 100 µm.