7 research outputs found
Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids
Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a
powerful tool for modeling brain development and neurological disorders. Rett syndrome
(RTT), a rare neurodevelopmental disorder, can greatly benefit from this technology,
since it affects multiple neuronal subtypes in forebrain sub-regions. We have established
dorsal and ventral forebrain organoids from control and RTT patient-specific hiPSCs
recapitulating 3D organization and functional network complexity. Our data revealed
a premature development of the deep-cortical layer, associated to the formation of
TBR1 and CTIP2 neurons, and a lower expression of neural progenitor/proliferative
cells in female RTT dorsal organoids. Moreover, calcium imaging and electrophysiology
analysis demonstrated functional defects of RTT neurons. Additionally, assembly of
RTT dorsal and ventral organoids revealed impairments of interneuron’s migration.
Overall, our models provide a better understanding of RTT during early stages of
neural development, demonstrating a great potential for personalized diagnosis and
drug screening