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In this study, personalized dorsal and ventral forebrain organoids (DFOs\/VFOs) are generated derived from brain astrocytes of patients with FCD type II (FCD II). The pathological features of dysmorphic neurons, balloon cells, and astrogliosis are successfully replicated in patient\u2010derived DFOs, but not in VFOs. It is noteworthy that cardiomyocyte\u2010like cells correlated with dysmorphic neurons are generated through the high activation of BMP and WNT signaling in some of the FCD\u2010organoids and patient cortical tissues. Moreover, functional assessments demonstrated the occurrence of epileptiform burst firing and propagative self\u2010assembling neuronal hyperactivity in both FCD\u2010DFOs and VFOs. Additionally, the heterotopic cardiomyocyte\u2010organoids demonstrated the capacity for cardiomyocyte contraction and rhythmic firing. The presence of these cardiomyocytes contributes to the hyperactivity of neural networks in cardioids\u2010DFOs assembly. In conclusion, the personalized region\u2010specific forebrain organoids derived from FCD patient astrocytes effectively recapitulate heterogeneous pathological features, offering a valuable platform for the development of precise therapeutic strategies.<\/jats:p>","DOI":"10.1002\/advs.202409774","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T22:50:16Z","timestamp":1735685416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Personalized Human Astrocyte\u2010Derived Region\u2010Specific Forebrain Organoids Recapitulate Endogenous Pathological Features of Focal Cortical Dysplasia"],"prefix":"10.1002","volume":"12","author":[{"given":"Jinhong","family":"Xu","sequence":"first","affiliation":[{"name":"Institute for Translational Brain Research State Key Laboratory of Medical Neurobiology MOE Frontiers Center for Brain Science Institute of Pediatrics National Children's Medical 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