ID: hyp-SDA-2026-04-08-gap-pubmed-20260406-0
Hypothesis
Epigenetic SPI1 Reprogramming Therapy
Chronic vascular inflammation epigenetically reprograms SPI1 chromatin accessibility, maintaining persistent neuroinflammatory gene expression even after vascular insult resolution.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
Chronic vascular inflammation epigenetically reprograms SPI1 chromatin accessibility, maintaining persistent neuroinflammatory gene expression even after vascular insult resolution. Targeted epigenetic editing to reset SPI1 binding landscapes could reverse pathological microglial activation states.
🧬 Mechanism
🔗 Mechanism from KG for SPI1
Auto-built from this analysis's top knowledge-graph edges.
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"]
SPI1_16["SPI1"] -->|regulates| Inflammatory_gene_express["Inflammatory gene expression"]
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
style SPI1_16 fill:#ce93d8,stroke:#333,color:#000
style Inflammatory_gene_express fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
⚖️ Evidence Matrix5 supports0 contradicts
Supports
Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.
Supports
Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.
Supports
Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals.
Supports
Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — SPI1
No curated PDB or AlphaFold mapping for SPI1 yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for SPI1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0530
Events (7d)
0
Price History
▲5.8%💾 Resource Usage
LLM Tokens
10,898
$0.0654
Total Cost
$0.0654
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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