Extended Data Fig. 2: scRNA-seq analysis reveals NNMT expression across all CAF subtypes.
From: NNMT inhibition in cancer-associated fibroblasts restores antitumour immunity
a, Dot plot showing canonical marker expression across different cell types in scRNA-seq data from omental metastases of chemotherapy-naïve HGSOC patients (n = 7). Genes used for CAF annotation are listed in Supplementary Table 5. SMC = smooth muscle cells, Adipo/Endo cells = adipocytes/endothelial cells. b, Distribution of patient samples across all major cell types. Total cell numbers per cell type are shown in brackets. CN = chemotherapy naïve. c, Gene ontology enrichment analysis based on the Biological Processes dataset of the identified CAF subsets: inflammatory CAFs (iCAFs), vascular CAFs (vCAFs), proliferative CAFs (prolCAFs), antigen-presenting CAFs (apCAFs), oxidative phosphorylation CAFs (OXPHOS CAFs), myofibroblastic CAFs (myCAFs), neural CAFs, and developmental CAFs (devCAF) (Hypergeometric test with Benjamini-Hochberg FDR correction). ag = antigen. d, Top 200 overexpressed genes of the respective CAF subtypes from (c) are highlighted (scaled mean expression) (two-tailed Wilcoxon Rank Sum test with Benjamini-Hochberg FDR correction) (Supplementary Table 6). e, Gene Set Enrichment Analysis of established CAF subtype signatures in the spatial transcriptomics data of NNMThigh (n = 24) versus NNMTlow (n = 16) ovarian cancer stroma. Gene sets are based on Chhabra and Weeraratna (2023)3 (Supplementary Table 7). FDR = false discovery rate, NES = normalized enrichment score. f, scRNA-seq dataset published by Luo et al.21 (https://gist-fgl.github.io/sc-caf-atlas/; https://creativecommons.org/licenses/by/4.0/). Uniform Manifold Approximation and Projection (UMAP) of cancer types (left panel), cell type annotation (middle panel), NNMT expression (right panel). OVCA = ovarian cancer, PDAC = pancreatic ductal adenocarcinoma, LUAD = lung adenocarcinoma, BLCA = urinary bladder cancer, GC = gastric cancer, BRCA = breast cancer, LC = liver cancer, PRAD = prostate cancer, CRC = colorectal cancer, ICC = intrahepatic cholangiocarcinoma, THCA = thyroid cancer. g, scRNA-seq dataset published by Ma et al.22 (https://chenxisd.shinyapps.io/pancaf/; https://github.com/SGDDNB/ShinyCell (GPL-3.0)). UMAP of cancer types (left panel), CAF subtype annotation (middle panel), NNMT expression (right panel). BRCA = breast cancer, LIHC = liver hepatocellular carcinoma, PRAD = prostate adenocarcinoma, OVCA = ovarian cancer, CRC = colorectal cancer, UCEC = uterine corpus endometrial carcinoma, SMC = smooth muscle cells, iCAF = inflammatory CAFs, pCAF = proliferative CAFs, mCAF = matrix CAFs, meCAF = metabolic CAFs.
