Fig 2: The expansion and activation of MDSCs in patients with MALT lymphoma. (A) The proportion of myeloid-derived suppressor cells (MDSCs) in CD45+ peripheral blood mononuclear cells (PBMCs) is higher in newly diagnosed mucosa-associated lymphoid tissue (MALT) lymphoma patients (n = 8) compared to age-matched controls (n = 12); **P < 0.01. (B) Representative flow cytometric dot plots showing MDSCs in the peripheral blood of a patient and age-matched healthy individual. (C) Representative immunofluorescence images of CD11b+CD33+ MDSCs in gastric MALT lymphoma and paired normal tissues. Red, CD11b; green, CD33; and blue, 4′ ,6-diamidino-2-phenylindole (DAPI); original magnification, 400×. (D) Quantitative analysis of MDSCs (CD11b+CD33+) in gastric MALT lymphoma and paired normal tissues; **P < 0.01. (E) Representative immunohistochemistry (IHC) images of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS) in gastric MALT lymphoma and paired normal tissues. Original magnification, 400×. (F) Histoscores of Arg-1 and iNOS were higher in gastric MALT lymphoma tissues compared to control; **P < 0.01, *P < 0.05.

Fig 3: Stromal biglycan inhibition suppresses lung metastasis, by normalizing tumor vasculature in breast cancer. a Growth curves of E0771 tumor growth in WT and Bgn KO mice measured every 4 days. b Comparison of E0771 tumor weight at day 24 after inoculation. c Representative IVIS images and quantitative analysis of metastatic lungs in E0771 tumors of WT versus Bgn KO mice. d Bgn mRNA expression in E0771 tumor tissues of WT and Bgn KO mic analyzed by quantitative real-time RT-PCR. e Biglycan concentration in mouse plasma from non-tumor WT mice, E0771 tumor-bearing WT mice, and E0771 tumor-bearing Bgn KO mice detected by ELISA. f Immunofluorescent images of biglycan (green) expression in CD31+ blood vessels (red) in E0771 tumors grown in WT mice. DAPI, blue. Scale bar = 20 μm. g Bgn mRNA expression in FACS isolated CD31− cells, CD45− CD31+ cells (E0771-TECs), and dermal ECs from naïve mice by quantitative real-time RT-PCR. h Representative images of CD31+ blood vessels in E0771 tumors from WT and Bgn KO mice. Scale bar = 100 μm. i Quantification of blood vessel density. j Representative images of CD31 immunostaining (red), ɑ-SMA (green), and DAPI nuclear staining (blue) in E0771 tumors from WT and Bgn KO mice. Scale bar = 100 μm. k Quantification of ɑ-SMA+ CD31+ tumor blood vessels. The rate of microvessel pericyte coverage was analyzed by counting the vessels that stained positive for both CD31 and α-SMA (white arrowheads) among CD31-positive vessels. l Representative images of CD31 immunostaining (red), FITC-lectin (green), and DAPI (blue) in E0771 tumors from WT and Bgn KO mice. Scale bar = 100 μm. m Quantification of lectin+ blood vessels. The rate of lectin+ blood vessels was analyzed by counting the vessels that stained positive for both CD31 and lectin (white arrowheads) among CD31-positive vessels. n Representative images of CD31 immunostaining (green), Glut1 (red), and DAPI (blue) in E0771 tumors from WT and Bgn KO mice. Scale bar = 100 μm. o Quantification of Glut1+ area. *p < 0.05, ***p < 0.001. Significance in b, d, i, k, m, and o were determined by a two-tailed Student’s t test. Significance in g was determined by a one-way ANOVA. All data represent means ± SD

Fig 4: Droplet-based single-cell assays for transposase-accessible chromatin sequencing (scATAC-seq) analysis of thymic epithelial cells (TECs) in 4-week mice.(A) Uniform manifold approximation and production (UMAP) plot of scATAC-seq data from TECs (EpCAM+ CD45– TER119–) from 4-week mice. Cell clusters are separated by colors and numbers in the plot. The two datasets were integrated using the Seurat package. The graph on the right shows percentages of each cluster in the total number of cells detected (15,255 cells). (B) Chromatin accessibility of typical marker genes of TECs. Accessibility in each gene region is represented in red. (C) Violin plot depicting chromatin accessibility in Aire and Cd80 gene regions in each cluster. (D) Pseudo-bulk accessibility tracks of the Aire gene region in each cluster (upper panels) and frequency of sequenced fragments within the Aire gene region of individual cells in cluster 0, 2, and 4 (lower panels).

Fig 5: Dpp4+ progenitors give rise to ICAM1+/DPP4(−) preadipocytes in vivo. (A) Schematic depicting the lineage tracing timeline. Six-week-old Dpp4CreER; mGFP mice were injected with tamoxifen to produce heritable mGFP labeling of Dpp4+ cells. Lineage traced mice were placed on either chow or HFD at 8 weeks of age and harvested at 24 weeks. (B, C) Flow cytometric analysis of mGFP+ SVF cells from visceral (B) and subcutaneous (C) WAT of Dpp4CreER mice. CD45(−)/DAPI(−) SVF cells were gated on expression of mGFP to isolate lineage traced cells. Staining with anti-DPP4 and anti-ICAM1 at the pulse timepoint (left panel) and following 18 weeks of either chow diet (middle panel) or HFD (right panel). Data are representative of four biologic replicates. (D, E) Quantification of relative Dpp4+ lineage traced population abundance from visceral (D) and subcutaneous (E) WAT of Dpp4CreER; mGFP mice.