Advancing autism research: Insights from brain organoid modeling

Autism Spectrum Disorders (ASD) are characterized by a variety of behavioral symptoms and a complex genetic architecture, posing significant challenges in understanding the mechanistic processes underlying their pathology. Despite extensive research, the mechanisms linking genetic variations to the phenotypic outcomes associated with ASD remain elusive. Consistent evidence indicates disruptions in early brain development among individuals with ASD. The advent of brain organoids offers a unique opportunity for uncovering, how brain development changes in ASD patients. Brain organoids are three-dimensional in vitro model systems derived from pluripotent stem cells that recapitulate early human brain development across multiple biological levels. They have become an invaluable tool for studying human-specific brain development processes and neurodevelopmental disorders. In this review, we discuss recent findings using brain organoid technologies to model ASD and discuss, how these new technologies can enhance our understanding of ASD genetics and pathology at the molecular, cellular, and tissue levels. • Brain organoids model ASD at molecular, cellular, and tissue levels. • ASD organoids display altered cell cycles and neural progenitor proliferation. • ASD genetic perturbations exhibit cell type- and developmental stage-specific effects. • Cell-type specific behavior and neuronal networks can be modeled in ASD organoids. • Phenotypes in ASD organoids can be correlated with patient pathological features.