Personalized Human Astrocyte-Derived Region-Specific Forebrain Organoids Recapitulate Endogenous Pathological Features of Focal Cortical Dysplasia.

ABSTRACT: Focal cortical dysplasia (FCD) is a highly heterogeneous neurodevelopmental malformation, the underlying mechanisms of which remain largely elusive. 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-derived DFOs, but not in VFOs. It is noteworthy that cardiomyocyte-like cells correlated with dysmorphic neurons are generated through the high activation of BMP and WNT signaling in some of the FCD-organoids and patient cortical tissues. Moreover, functional assessments demonstrated the occurrence of epileptiform burst firing and propagative self-assembling neuronal

SUBMITTER: Xu J 

PROVIDER: S-EPMC11848560 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature