Loss of MAP4K4 expression affects apoptosis during the process of neutrophil differentiation.
<p>(A) UMAP plot of the neutrophil co-expression network. Each node represents a single gene, and edges represent co-expression links between genes and module hub genes. Point size is scaled by eigengene-based connectivity (kME). Nodes are colored by co-expression module assignment. The top fi...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , |
| منشور في: |
2025
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| الموضوعات: | |
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إضافة وسم
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| الملخص: | <p>(A) UMAP plot of the neutrophil co-expression network. Each node represents a single gene, and edges represent co-expression links between genes and module hub genes. Point size is scaled by eigengene-based connectivity (kME). Nodes are colored by co-expression module assignment. The top five hub genes per module are labeled. Network edges were down-sampled for visual clarity. (B) Heatmap of scaled gene expression for the top 10 hub genes by kME in each module. (C) UMAP colored by Pseudotime. (D) UMAP colored by harmonized module eigengenes (hMEs) of each module. (E) Module eigengenes (MEs) as a function of pseudotime for each co-expression module. For each module, a separate loess regression line is shown for each condition. The p value was calculated by distance correlation t-test (dcorT.test). dcor is a transformation of a bias-corrected version of distance correlation. The smaller the dcor, the greater the distance between control (Ctrl) and <i>Map4k4</i>-cKO (cKO) conditions. (F) Differentially expressed hub genes between control (Ctrl) and <i>Map4k4</i>-cKO (cKO) parasites involved in positive regulation of apoptotic process determined by Gene Set Enrichment Analysis (GSEA). RES represents the running enrichment score. RLM represents the ranked list metric. (G) Violin plots of apoptosis scores of control (Ctrl) against <i>Map4k4</i>-cKO (cKO) for each cluster, the p value was calculated by the Student’s t-test. (H) Percentages of annexin V<sup>+</sup> and SYTOX<sup>−</sup> cells in bone marrow neutrophil progenitor cells of control (Ctrl) or <i>Map4k4</i>-cKO (cKO) mice; MM, metamyelocytes; BC/SC, band cells and segmented neutrophils; BM, bone marrow (n=10; mean ± SD). Mann-Whitney U test. (I) Percentages of annexin V<sup>+</sup> and SYTOX<sup>−</sup> cells of HL-60 cells treated with 0-20 µM MAP4K4 inhibitor (PF-06260933, PF) for 48 hours, followed by a subsequent 96-hour treatment with both PF and all-trans-retinoic acid (ATRA) (n=4; mean ± SD). Mann-Whitney U test. (J) Quantification of HL-60 cell numbers after a 48-hour treatment with a 10 µM concentration of the MAP4K4 inhibitor (PF-06260933, PF), followed by a subsequent 96-hour treatment with both PF and all-trans-retinoic acid (ATRA) (n=4; mean ± SD). Mann-Whitney U test.</p> |
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