Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids.

ABSTRACT: Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy. Compared to isogenic controls, we found abnormal neuronal activity in Rett organoids and altered network function based on graph theoretic analyses, with V247X mutations impacting functional responses and conne

SUBMITTER: Osaki T 

PROVIDER: S-EPMC11326256 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature