SPI1-Mediated Metabolic Reprogramming in Neuroinflammation

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How does SPI1 transcriptionally regulate C1QA and C1QC expression in atherosclerotic contexts?

The authors identify SPI1 as a potential transcription factor regulating the hub genes but provide no mechanistic details of this regulatory relationship. Given SPI1's role in microglial activation and neuroinflammation, this regulatory circuit may be relevant to cerebrovascular disease and neurodegeneration. Gap type: unexplained_observation Source paper: An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis. (2023, Front Immunol, PMID:38179058)

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graph TD
    SPI1["SPI1"] -->|encodes| PU_1["PU.1"]
    SPI1_1["SPI1"] -->|regulates| C1Q["C1Q"]
    SPI1_2["SPI1"] -->|contributes to| neuroinflammation["neuroinflammation"]
    SPI1_3["SPI1"] -->|regulates| glycolytic_metabolism["glycolytic_metabolism"]
    SPI1_4["SPI1"] -->|regulates| microglia["microglia"]
    C1Q_5["C1Q"] -->|enhances| SPI1_6["SPI1"]
    SPI1_7["SPI1"] -->|causes| neuroinflammatory_memory["neuroinflammatory_memory"]
    SPI1_8["SPI1"] -.->|inhibits| synaptic_plasticity["synaptic_plasticity"]
    SPI1_9["SPI1"] -->|orchestrates| neurovascular_unit["neurovascular_unit"]
    SPI1_10["SPI1"] -->|amplifies| neuroinflammation_11["neuroinflammation"]
    SPI1_12["SPI1"] -->|modulates| chromatin_accessibility["chromatin_accessibility"]
    chronic_vascular_inflamma["chronic_vascular_inflammation"] -->|regulates| SPI1_13["SPI1"]
    SPI1_14["SPI1"] -->|maintains| microglial_activation["microglial_activation"]
    SPI1_15["SPI1"] -->|associated with| atherosclerosis["atherosclerosis"]
    style SPI1 fill:#ce93d8,stroke:#333,color:#000
    style PU_1 fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_1 fill:#ce93d8,stroke:#333,color:#000
    style C1Q fill:#ce93d8,stroke:#333,color:#000
    style SPI1_2 fill:#ce93d8,stroke:#333,color:#000
    style neuroinflammation fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_3 fill:#ce93d8,stroke:#333,color:#000
    style glycolytic_metabolism fill:#81c784,stroke:#333,color:#000
    style SPI1_4 fill:#ce93d8,stroke:#333,color:#000
    style microglia fill:#4fc3f7,stroke:#333,color:#000
    style C1Q_5 fill:#ce93d8,stroke:#333,color:#000
    style SPI1_6 fill:#ce93d8,stroke:#333,color:#000
    style SPI1_7 fill:#ce93d8,stroke:#333,color:#000
    style neuroinflammatory_memory fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_8 fill:#ce93d8,stroke:#333,color:#000
    style synaptic_plasticity fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_9 fill:#ce93d8,stroke:#333,color:#000
    style neurovascular_unit fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_10 fill:#ce93d8,stroke:#333,color:#000
    style neuroinflammation_11 fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_12 fill:#ce93d8,stroke:#333,color:#000
    style chromatin_accessibility fill:#4fc3f7,stroke:#333,color:#000
    style chronic_vascular_inflamma fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_13 fill:#ce93d8,stroke:#333,color:#000
    style SPI1_14 fill:#ce93d8,stroke:#333,color:#000
    style microglial_activation fill:#4fc3f7,stroke:#333,color:#000
    style SPI1_15 fill:#ce93d8,stroke:#333,color:#000
    style atherosclerosis fill:#ef5350,stroke:#333,color:#000

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