{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:08:26Z","timestamp":1789740506863,"version":"4.0.1"},"reference-count":137,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Ischemic stroke remains a major cause of death and long-term disability and is defined by complex, dynamic pathophysiological processes involving diverse cell types and interconnected molecular networks. In recent years, single-cell and single-nucleus RNA sequencing (sc\/snRNA-seq) have provided unmatched resolution for dissecting these processes. A growing body of studies has applied these approaches to ischemic stroke, generating extensive insight into cellular heterogeneity, molecular regulation, and disease-associated cell states. This review systematically integrates current evidence from sc\/snRNA-seq studies, with a primary focus on brain-intrinsic mechanisms after ischemic stroke. Existing findings are organized across major pathophysiological domains, including immune and inflammatory responses, blood-brain barrier (BBB) disruption and angiogenesis, regulated cell death, metabolic dysregulation, aging and cellular senescence, and neuroregeneration and remyelination. Beyond these canonical mechanisms, we summarize emerging applications of sc\/snRNA-seq in extra-CNS systems, distinct biological contexts, and stroke-related complications. We also highlight how sc\/snRNA-seq has been used to investigate therapeutic mechanisms, including physical and neuromodulatory interventions, pharmacological agents, cell-based therapies, and bioengineered delivery systems. Together, this review provides a structured synthesis of how sc\/snRNA-seq has advanced the understanding of ischemic stroke biology by identifying disease-relevant cell states, refining mechanistic targets, and informing future translational development.<\/jats:p>","DOI":"10.3389\/fneur.2026.1890630","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:46:01Z","timestamp":1789739161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell and single-nucleus transcriptomics in ischemic stroke: cellular mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Changqing","family":"Mu","sequence":"first","affiliation":[{"name":"Luhe Institute of Neuroscience, Capital Medical University","place":["Beijing, China"]},{"name":"Department of Neurology, Beijing Luhe Hospital, Capital Medical University","place":["Beijing, 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