Journal: Clinical and Molecular Hepatology

Article Title: COLEC12 high tumor-associated macrophages orchestrate lenvatinib resistance and cancer stemness in hepatocellular carcinoma via paracrine NRG1-HER2/HER3 signaling

doi: 10.3350/cmh.2025.1059

Figure Lengend Snippet: NRG1 mediates COLEC12 high TAM-induced stemness and therapeutic resistance. (A) Overlap of genes upregulated in COLEC12 OE macrophages with the THPA secretome. Heatmap of the top 20 induced genes. qRT-PCR, immunoblot, and ELISA confirm increased NRG1 expression and secretion in COLEC12 OE THP-1 macrophages (n=3). (B) COLEC12 OE CM increases lenvatinib resistance in Huh7 cells, whereas NRG1 knockdown reverses this effect, as shown by IC50, CCK-8 proliferation, colony formation, and apoptosis assays (n=3). (C) Subcutaneous Huh7 xenografts (n=6) and orthotopic liver models were treated with intratumoral or intraperitoneal injections of Vector-CM, COLEC12 OE -CM, or COLEC12 OE +shNRG1#1-CM with/without lenvatinib, showing tumor images, volumes, weights, and liver/body weight ratios (n=6). (D) qRT-PCR of SOX2/OCT4/CD44/CD133 in Huh7 under indicated CM (n=3). Tumorsphere formation under indicated CM (n=3). (E) Limiting dilution assays in vitro (M, n=3) and in vivo (N, n=6 per group), showing stem cell or tumor-initiating frequencies. Data are presented mean±standard error of the mean. Two group comparisons used Student’s t-test; multiple groups used one-way ANOVA; tumor initiation used Kruskal–Wallis. NRG1, Neuregulin 1; COLEC12, Collectin Subfamily Member 12; THPA, The Human Protein Atlas ; CM, conditioned medium; COLEC12 OE , COLEC12-overexpressing. * P <0.05, ** P <0.01, *** P <0.001. Source data available.

Article Snippet: We integrated COLEC12 OE macrophage transcriptomic data with the secretome dataset from The Human Protein Atlas (THPA) to identify potential mediators of COLEC12 high macrophage–induced stemness in HCC.

Techniques: Quantitative RT-PCR, Western Blot, Enzyme-linked Immunosorbent Assay, Expressing, Knockdown, CCK-8 Assay, Plasmid Preparation, In Vitro, In Vivo

Journal: bioRxiv

Article Title: A Rare Multipotent Peg-like Epithelial Cell is a Candidate Cell-of-Origin for High-Grade Serous Ovarian Cancer

doi: 10.1101/2025.09.23.677404

Figure Lengend Snippet: (A) Overview of proteomic and secretome datasets generated from biobank specimens and utilized from public sources. (B) Experimental workflow for identifying secreted molecules across the FT epithelium and their subclusters. (C and D) Venn diagrams comparing protein overlap between datasets: tissue secretome vs. public FT lavage secretome ( C ), and tissue secretome vs. EpCAM⁺ Lin - cell proteome ( D ). (E) Venn diagram showing overlap between the inferred EpCAM⁺ Lin - cell secretome (shared proteins from tissue secretome and EpCAM⁺ proteome) and the secretome of 2D-cultured cells. (F) UMAP of the integrated epithelial subset showing expression of a signature derived from all genes encoding proteins found in the EpCAM⁺ cell proteome. (G) UMAP displaying expression of a refined signature representing overlapping genes from the tissue secretome and EpCAM⁺ cell proteome. (H) Bar plot quantifying the number of secreted molecules from the tissue secretome detected across epithelial subclusters. (I) Electron microscopy (EM) image of an FT organoid showing secretory granules along the apical surface of multiciliated and secretory cells. Annotations: C = cilia; MV = microvilli; S = secretory granules. Scale bar, 10 µm. (J) Table listing the top 20 differentially expressed secretory molecules from each epithelial subcluster. Color shading reflects the presence of each gene’s protein product in the proteome and/or secretome datasets shown in panel B , indicating relative support across modalities. See Supplementary Figure 6 for additional related data .

Article Snippet: A comprehensive reference list of human secreted proteins was compiled from multiple sources: (1) Human Protein Atlas (HPA) secretome datasets across diverse tissues, (2) reviewed UniProt entries annotated as secreted, (3) FT lavage proteome data, (4) 2D cultured PAX8+ epithelial cell secretome, (5) 2D cultured P0 FT epithelial cell secretome (6) fresh tissue secretome, (7) FT EpCAM+ cell proteome, (8) FT 3D organoid proteome and (9) a published FT proteome.

Techniques: Generated, Cell Culture, Expressing, Derivative Assay, Electron Microscopy