{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:54:34Z","timestamp":1781592874405,"version":"3.54.5"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Focal cortical dysplasia (FCD) is a leading cause of drug\u2010resistant epilepsy, whereas its molecular and cellular mechanisms remain poorly understood. This study aimed to characterize the cellular heterogeneity of FCD and investigate the function of ferroptosis in FCD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010nucleus RNA sequencing was carried out on epileptogenic cortical tissues from 18 patients with FCD and 6 perilesional control samples with normal histology. Data were analysed using uniform manifold approximation and projection for dimensionality reduction and visualization. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. UCell scoring and gene set enrichment analysis (GSEA) were applied to assess pathway activity. Expression levels of ferroptosis\u2010related genes (FRGs) were validated by immunofluorescence, and biochemical assays quantified the levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lipid peroxides (LPO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 170\u00a0747 nuclei were profiled, resolving five major cell types, including inhibitory neurons, excitatory neurons, astrocytes, microglia and oligodendrocytes. DEGs across these populations were significantly enriched in ferroptosis and oxidative stress\u2013associated pathways. UCell and GSEA highlighted remarkable alterations in ferroptosis, apoptosis and oxidative stress, particularly in inhibitory neurons and astrocytes. Immunofluorescence confirmed upregulation of key FRGs, including ferritin light chain, ferritin heavy chain 1, poly rC binding protein 1, microtubule\u2010associated protein 1 light chain 3B and prion protein\u2010encoding gene, in FCD tissues. Concordantly, biochemical assays demonstrated reduced SOD and GSH levels, alongside elevated MDA and LPO levels, confirming the transcriptional and histological findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results indicated that ferroptosis may play a notable role or act as a concurrent mechanism in the pathogenesis of FCD, potentially contributing to the neuronal and glial dysfunction and epileptogenesis. Integrating transcriptomic, histological and biochemical data, this study demonstrated that targeting ferroptosis\u2010related pathways may hold promise as a potential therapeutic strategy for FCD, providing new insights into the molecular mechanisms underlying this condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This study pioneers the first single\u2010nucleus transcriptomic atlas for Focal Cortical Dysplasia (FCD) types I and II, deciphering the cellular heterogeneity across five major brain cell types within the epileptogenic cortex.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Through integrated multi\u2010omics analysis, it reveals for the first time a significant association between the ferroptosis pathway and FCD pathogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We identify and validate ferroptosis\u2010related genes (e.g.,\n                            <jats:italic>FTH1<\/jats:italic>\n                            ,\n                            <jats:italic>FTL<\/jats:italic>\n                            ,\n                            <jats:italic>PCBP1<\/jats:italic>\n                            ) as potential biomarkers and therapeutic targets, supported by congruent biochemical evidence of oxidative stress in this drug\u2010resistant epilepsy.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70668","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:43:25Z","timestamp":1777448605000},"source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010nucleus RNA sequencing reveals ferroptosis as a potential contributor to the pathogenesis of focal cortical dysplasia"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1831-212X","authenticated-orcid":false,"given":"Qingyang","family":"Zeng","sequence":"first","affiliation":[{"name":"Epilepsy Center and Department of Neurology Shenzhen Children\u2019s Hospital Shenzhen Guangdong China"},{"name":"Shenzhen Pediatrics Institute Shantou University Medical College Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Epilepsy Center and Department of Neurology Shenzhen Children\u2019s Hospital Shenzhen Guangdong 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