Microglial involvement in autism spectrum disorder: insights from human data and iPSC models

Autism spectrum disorder (ASD) presents a range of lifelong challenges in social communication, repetitive behaviors, and restricted interests, affecting over 2% of the preschool population. Early neurodevelopmental disruptions, particularly those affecting microglia, appear to be central to the pathophysiology of ASD, with microglia influencing synaptic development and stability in the brain. However, the neurobiological mechanisms underlying ASD are still not fully understood. Traditional ASD studies, which rely on animal models and postmortem tissues, have limitations in capturing human-specific neurodevelopmental dynamics. Recent advances in human model systems, including induced pluripotent stem cell (iPSC)-derived neural cultures and brain organoids, offer promising insights into microglia-neuron interactions relevant to ASD. This review evaluates current research using human-based models to explore ASD pathophysiology, focusing on the role of microglia in neurodevelopment, and discusses the strengths and future potential of these innovative approaches.