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. 2021 Dec 20;12:809208. doi: 10.3389/fimmu.2021.809208

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Copyright © 2021 Yang, Wu, Sun, Fang, Liu, Ji, Park, Qin, Yang and Wang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Canonical pathway analysis for SDE genes in four comparison groups (Top 10 up/down changed pathways), (A). CT Ly6C^high vs CT Ly6C^low; (B). ApoE^-/- Ly6C^high vs ApoE^-/- Ly6C^low; (C). Ly6C^high (ApoE^-/- vs CT); (D). Ly6C^low (ApoE^-/- vs CT). Top up/down changed canonical pathways were identified by using IPA software with the criteria of adjusted P value<0.05. Blue bar indicates a negative z-score and down-regulated pathways. Red bar indicates a positive z-score and up-regulated pathways. Bold letters indicate overlapped pathway in the same subset. (E) Top 2 up/down regulated pathway. The most enriched significant pathways from GSEA study with threshold of |NES|>1.5 are marked (red=up-regulated, blue=down-regulated). The green curve corresponds to the enriched score. The y-axis indicates the enriched score. The x-axis displaces genes (vertical black lines) represented in their pathway gene set. Rainbow bands represent the corresponding enriched score of the genes (red for positive and blue for negative correlation). The top 20 upregulated or downregulated GSEA pathways were shown in Supplementary Table 1 . (F) Pathway overlap analysis and top 5 functional pathways. Venn diagram summarized the overlap of top 10 pathway presented in (A–D) and listed the top 5 pathways in four pairs of comparisons. (G) Model of signaling pathway in Ly6C MC subset (overlapped or top 5 pathway). Four activated pathways in Ly6C^high MC and 5 activated pathway in Ly6C^low MC were overlapped in A and B comparison. ApoE ^-/- induced top 5 activated pathway in both Ly6C^high MC and Ly6C^low MC. MC, monocyte; MΦ, macrophage; TREM1, The triggering receptor expressed on myeloid cells 1; GPCRs, G-protein-coupled receptors; PFKFB4, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4; SLE, Systemic Lupus Erythematosus, Th1, T helper 1; PKCθ, Protein Kinase C Theta; IL-7, Interleukin 7; NFAT, Nuclear factor of activated T-cells; CHK, Csk-homologous kinase; nNOS, neuronal nitric oxide synthase; PXR, pregnane X receptor; CAR, constitutive androstane receptor. NO, Nitric Oxide; ROS, Reactive Oxygen Species; PRRs, Pattern Recognition Receptors.