Fig. 2: LOY in malignant epithelial cells promotes anaerobic metabolic reprogramming and reduces immunogenicity.
From: Concurrent loss of the Y chromosome in cancer and T cells impacts outcome
a, scRNA-seq database constituted by 497,055 cells from 105 male tumour samples, coloured by six principal cell types (left) and 12 cancer types (right). b, LOYSCR predictions for cells in a. c, Mean expression (colour) and percentage of expressing cells (size) for the nine Y chromosome genes used in the Random Forest model, their X chromosome paralogues and GAPDH across different cell types and LOYSCR status. Paralogue gene pairs share colours. d, Database of 157,029 male epithelial cells, coloured by cancer type. e, Normalized enrichment scores (NES) for the top five upregulated and 15 downregulated pathways in LOYSCR versus WTYSCR epithelial cells, categorized into four functional groups. Bar colour denotes −log10-adjusted P value, calculated by gseGO in the clusterProfiler package. f, Glycolysis (left) and hypoxia (right) signatures in LOYSCR (n = 73,576) versus WTYSCR (n = 83,453) epithelial cells. Data are mean ± s.e.m.; two-sided Wilcoxon rank sum tests. g, MHC class I gene expression in LOYSCR versus WTYSCR epithelial cells. Dot plot (bottom) presentation as in c. Bars (top) show log2FC, with colours indicating −log10-adjusted P value, calculated with sc.tl.rank_genes_group in the scanpy package using two‐sided Wilcoxon rank‐sum test with Benjamini–Hochberg correction. h,i, Scores for proliferation-related (h) and genomic instability-related (i) pathways in LOYSCR versus WTYSCR epithelial cells. Dot colour represents mean scaled pathway score; dot size represents −log10 P value (two-sided Wilcoxon rank sum tests, Benjamini–Hochberg correction). j, GSEA pathway enrichment analysis of CRISPR Y-KO and CRISPR Y-Scr MB49 cells. NES > 0 indicates pathway enrichment in Y-KO cells. Statistics calculated as in e. k, Expression of genes related to genomic instability, cell cycle and antigen presentation in CRISPR Y-Scr (n = 3) and CRISPR Y-KO (n = 3) cells. Dots, replicates (mean ± s.e.m.); Student’s t-tests. BER, base excision repair; HDR, homology-directed repair; NER, nucleotide excision repair; NHEJ, non-homologous DNA end joining.
