Induced Pluripotent Stem Cells & Developmental Disorders
Over the last several years we derived more than 500 iPSC lines from patients with developmental disorders as a window into normal and abnormal neuronal development. We established protocols for converting iPSCs into brain organoids that reflect the human cerebral cortex, basal ganglia and other brain regions at prenatal stages of development. Using this model, our group has discovered neurodevelopmental alterations in autism spectrum disorders (Mariani et al, Cell, 2015) and Tourette syndrome (ongoing). As part of the PsychENCODE collaborative multi-site project, we generated a genome-scale catalog of enhancers and their associated gene targets active in early brain development (Amiri et al, Science, 2018). These data establish links between genes and enhancers active at embryonic and fetal stages of human development, and allow the study of risk alleles for human developmental disorders.