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ACVR1-mediated glycolytic reprogramming promotes histone lactylation and neuronal pyroptosis in neuropathic pain {ChIP-seq]

GSE306458 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 12 samples Submitted 2025/09/20 Platform GPL24247
Summary
Chronic neuropathic pain arises from intricate neuroimmune interactions, yet the molecular mechanisms remain poorly defined. Here, we identify activin A receptor type 1 (ACVR1) as a key neuronal driver of a metabolic-epigenetic program in the spinal dorsal horn following peripheral nerve injury. Nerve injury induced ACVR1 upregulation, which enhanced glycolytic flux and lactate production. Lactate served as a substrate for ACVR1-dependent histone H3 lysine 18 lactylation (H3K18la), an epigenetic modification enriched at promoters of pro-nociceptive genes, thereby activating a neuroinflammatory transcriptional program. Multi-omics integration and functional assays revealed that this pathway engaged the NLRP3 inflammasome and triggered neuronal pyroptosis. Pharmacological inhibition of ACVR1 or blockade of lactylation suppressed inflammasome activation, reduced neuroinflammation, and alleviated pain hypersensitivity in vivo. These findings delineate a pivotal neuronal ACVR1-glycolysis-H3K18la axis that orchestrates neuroimmune cross-talk in neuropathic pain, providing a potential metabolic-epigenetic target for therapeutic intervention.
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Direct links to NCBI, no account and no request form: the whole study as GSE306458_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1310864 and SRA study SRP613055. Searching any of these in the dataset finder brings you back here.

Study design
12 conditions, each sampled once — no replicated groups

Read from 12 sample titles: 12 distinct titles with little repetition. Check it against the sample list below before relying on it.

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