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Runx1 transcriptional regulation of microglia critically modulates opioid analgesia and withdrawal in humans and rodents [ChIP-seq]

GSE253851 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 3 samples Submitted 2026/01/30 Platform GPL24247
Summary
Opioid pain-relief and adverse outcomes differ between individuals. We show that runt-related transcription factor 1 (Runx1) is a determinant of opioid responses in humans and rodents and modulates the microglial transcriptome. Electron microscopy and single-cell RNA-sequencing revealed that deletion of Runx1 from microglia produces distinct ultra-structural and transcriptomic signatures. Microglia Runx1-deficient mice have reduced morphine potency, despite having no prior opioid exposure and normal nociceptive thresholds. These mice required greater amounts of post-operative morphine and displayed robust morphine-induced hyperalgesia and exacerbated withdrawal. In humans, genome-wide linkage analyses (GWAS) revealed variations within the Runx1 gene is associated with inter-individual differences in perioperative opioid requirement and opioid withdrawal severity. Identification of Runx1 susceptibility genotypes has implications for individualizing opioid pain management and determining risk of opioid dependence.
Published in
Runx1 transcription factor modulates opioid analgesia and withdrawal in humans and rodents
Leduc-Pessah H, McAllister BB, Sinha S et al. · Neuron 2026 · PMID 41619726 · doi:10.1016/j.neuron.2025.11.018
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Also filed as BioProject PRJNA1067575 and SRA study SRP485203. Searching any of these in the dataset finder brings you back here.

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