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EEG analysis suggests excitation-inhibition (E\/I) disbalance. However,\n                    <jats:italic>STXBP1<\/jats:italic>\n                    is ubiquitously expressed in all neuron types studied so far, and it remains unknown how haploinsufficiency leads to E\/I disbalance and\n                    <jats:italic>STXBP1<\/jats:italic>\n                    -RD symptoms. Here, we used single-cell RNA-sequencing to characterize the effect of\n                    <jats:italic>Stxbp1<\/jats:italic>\n                    haploinsufficiency across all brain cell types in the somatosensory cortex of a validated mouse model. We observed that the relative abundance of cell types was normal. The most prominent transcriptomic changes occurred in GABAergic and glutamatergic neurons, especially Sncg interneurons and deep-layer pyramidal neurons. Astrocytes exhibited substantial changes despite not expressing\n                    <jats:italic>STXBP1<\/jats:italic>\n                    , suggesting a non-cell autonomous response. Differentially expressed genes showed little overlap between neuronal types but accumulated in synaptic and translation-related GO terms. This was accompanied by a strong trend towards reduced protein translation as measured by puromycin incorporation. Excitatory neurons showed greater synaptic dysregulation than inhibitory neurons. Notably, neuronal transcriptome changes greatly overlapped with prior proteomics\n                    <jats:italic>STXBP1<\/jats:italic>\n                    -RD data but differed radically from other disorders. Seizure burden correlated negatively in astrocytes and neurons to expression of translation-related genes. These findings identify cell-type specific vulnerabilities to\n                    <jats:italic>STXBP1<\/jats:italic>\n                    haploinsufficiency which may explain hyperexcitability, network dysfunction and cognition deficits in\n                    <jats:italic>STXBP1<\/jats:italic>\n                    -RD. Overall, our study provides a cellular-resolution map of the transcriptomic changes in\n                    <jats:italic>STXBP1<\/jats:italic>\n                    -related disorders, providing potential new therapeutic targets.\n                  <\/jats:p>","DOI":"10.1038\/s41380-026-03869-w","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:27:22Z","timestamp":1790011642000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single cell RNA-sequencing reveals neuron type-specific vulnerabilities in a model of STXBP1-related disorder"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-8365","authenticated-orcid":false,"given":"A.","family":"Roig Adam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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