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. 2023 Jul 17;131(7):077006. doi: 10.1289/EHP12259

Figure 8.

Figure 8A is a Venn diagram displaying two circles. On the left, the circle is labeled Particulate matter exposure differentially expressed genes and, on the right, the circle is labeled Nicotinamide mononucleotide treatment differentially expressed genes. The intersection area is labeled as rescue differentially expressed genes. Figure 8B is a rose diagram displaying twelve cell types, namely, Alveolar macrophages, Neutrophils, T cells, B cells, Monocytes, Fibroblasts, Dividing dendritic cells, N K cells, Conventional dendritic cells, Clara cells, A T 2, and A T 1. A scale ranges from 0 to 150 in increments of 50. Figure 8C is a tabular representation with two main columns, namely, Cell type and The number of differentially expressed genes. The number of differentially expressed genes column is subdivided into three columns, namely, Rescue, Particulate matter exposure, and Nicotinamide mononucleotide treatment. Row 1: alveolar macrophages, 18, 31, and 69. Row 2: neutrophils, 135, 211, 256. Row 3: T cells, 14, 20, 60. Row 4: B cells, 25, 35, 48. Row 5: monocyte-derived cells, 34, 60, 120. Row 6: Fibroblasts, 83, 289, 377. Row 7: Dividing dendritic cells, 9, 25, 57. Row 8: N K cells, 5, 12, 36. Row 9: conventional dendritic cells, 1, 5, 4. Row 10: Clara cells, 0, 2, 21. Row 11: A T 2, 0, 1, 0. Row 12: A T 1, 0, 0, 0. A scale ranges from 50 to 350 in increments of 150. Figure 8D is a heatmap, plotting aryl hydrocarbon receptor signaling, pulmonary fibrosis idiopathic signaling pathway, interleukin-17 signaling, tumor microenvironment pathway, L X R or R X R activation (y-axis) across neutrophils, monocyte-derived cells, and fibroblasts (x-axis). A scale ranges from negative 2 to 2 in unit increments. Figure 8E is a stained tissue displaying three columns, namely, Air-filtered control - water, PM-exposed - water, and Exposure of nicotinamide mononucleotide and two rows, namely, Abca1 and Pltp. Figures 8G and 8H are bar graphs titled Plasma triglyceride and Liver triglyceride, plotting plasma triglyceride (millimoles per liter), ranging from 0.0 to 1.0 in increments of 0.2 and liver triglyceride (micromoles per milligram protein), ranging from 0.0 to 0.8 in increments of 0.2 (y-axis) across air-filtered control and PM exposure (x-axis) for water and nicotinamide mononucleotide, respectively. Figure 8F is a stained tissue displaying three columns, namely, Air-filtered control - water, PM-exposed - water, and Exposure of nicotinamide mononucleotide and four rows, namely, Maf, Fkbp5, Cebpb, and C5ar1.

NMN supplementation and markers of lipid metabolism in critical cell clusters in mice exposed to PM. (A) Schematic Venn diagram of overlapping “rescue” DEGs identified by integration analysis between “PM Exposure DEGs” (Exp-H2O vs. Con-H2O) and “NMN Treatment DEGs” (Exp-NMN vs. Exp-H2O). The corresponding data are shown in Excel Table S6. (B) Identified “rescue” DEGs of each cell cluster are visualized in a rose diagram. (C) The bubble matrix displays the numbers of “rescue” DEGs (Rescue), “PM Exposure DEGs” (PM Exposure) and “NMN Treatment DEGs” (NMN Treatment). (D) The heatmap illustrates the overlapping enriched canonical pathways analyzed using Ingenuity Pathway Analysis (IPA) software (Qiagen) among neutrophils, monocyte-derived cells, and fibroblasts based on “rescue” DEGs. The z-scores, from the lowest to the highest, are colored from blue to red, whereas a cross indicates when z-scores were unable to be calculated owing to a lack of sufficient evidence. The corresponding z-scores for each enriched pathway of the respective cell clusters are displayed in Table S9. (E) The expression of Pltp and Abca1 in fibroblast subsets of mouse lungs from Con-H2O, Exp-H2O, and Exp-NMN groups are shown in UMAP plots. (F) The expression of Maf, Fkbp5, Cebpb, and C5ar1 in monocyte-derived cell subsets of mouse lungs from Con-H2O, Exp-H2O, and Exp-NMN groups are shown in UMAP plots. The triglyceride (TG) levels examined in (G) mouse plasma (n=4/group) and (H) mouse liver tissues (n=4/group) from the Con-H2O, Exp-H2O, Con-NMN, and Exp-NMN groups, respectively, at the end of the subchronic PM exposure. The expression levels of genes in (E) and (F) are listed in Excel Table S11. Data in (G) and (H) were analyzed using one-way ANOVA followed by Tukey’s multiple comparison post hoc test. The results are presented as mean±SD. The mean, SD, and SEM values of the bar graphs in (G) and (H) are summarized in Table S5. **p<0.01, compared with Con-H2O mice. #p<0.05 compared with the Exp-H2O mice (Exp-NMN vs. Exp-H2O). p-Values for all tests are shown in Table S6. Note: AM, alveolar macrophages; ANOVA, analysis of variance; AT1, type 1 alveolar epithelial cells; AT2, type 2 alveolar epithelial cells; Con, air-filtered control group; DC, dendritic cells; DEGs, differentially expressed genes; dividing DC, dividing dendritic cells; Exp, PM exposure group; H2O, water; IL, interleukin; LXR, liver X receptor; NMN, nicotinamide mononucleotide; PM, particulate matter; RXR, retinoid X receptor; SD, standard deviation; SEM, standard error of the mean; UMAP, Uniform Manifold Approximation and Projection.