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Neural stem cells (NSCs) in the adult brain possess the potential to generate new neurons after injury, yet the molecular mechanisms regulating their neuronal differentiation following ischemic insult remain incompletely understood. Here, integrating single\u2010cell multi\u2010omics analyses with spatial transcriptomics, we systematically delineated cell type\u2010specific spatiotemporal dynamics in the striatum of a mouse model of ischemia\u2010reperfusion injury. We identified Neurensin 1 (Nrsn1) as a gene markedly upregulated during NSC\u2010derived neuronal differentiation in the recovery phase. Mechanistically, Foxa2 directly activates Nrsn1 transcription, whereas Nrsn1 promotes neuronal differentiation by facilitating the nuclear translocation of the chromatin\u2010remodeling factor Smarcc1 in vitro. In vivo, both endogenous NSCs and transplanted NSCs overexpressing Nrsn1 significantly enhanced neuronal regeneration and improved functional recovery in mice subjected to middle cerebral artery occlusion and reperfusion (MCAO\/R). Collectively, these findings identify Nrsn1 as a key regulator of NSC neuronal differentiation and uncover a Nrsn1\u2013Smarcc1 coupling mechanism that promotes neural regeneration after ischemic brain injury, highlighting a potential molecular target for strategies aimed at enhancing post\u2010stroke recovery.<\/jats:p>","DOI":"10.1002\/advs.77547","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:57:25Z","timestamp":1788497845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nrsn1\u2013Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic\u2010phase Recovery After Ischemic Stroke"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0462-0955","authenticated-orcid":false,"given":"Ruolin","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Biomedicine and Health College of Life science and Technology Huazhong 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