Figure 2.

Key elements in the process of modeling brain disorders using induced pluripotent stem cells (iPSCs). Clockwise from top of the circle (arrows): patient cohorts, generating iPSCs and differentiating neural cells in vitro, studying disease-relevant cellular phenotypes, and high-throughput assays for drug discovery. (Top panel) For comparing healthy versus diseased groups, shown are examples of patient cohorts, such as those within families, or those that are treatment-responsive or -resistant, or comparing cohorts of gene-edited cells containing disease-associated variants. (Right panel) Differentiating iPSCs into diverse disease-relevant neural cell types from different patient cohorts enables in vitro analysis of cellular phenotypes. (Bottom panel) Various cellular assays can be used to examine cellular functions and phenotypes in vitro. For example, neuron–astrocyte interactions via coculture, neuronal activity patterns, and phagocytic properties of microglia can be examined in vitro. (Left panel) Drug-response profiles of patient-cells can be measured in vitro. Patient iPSC-derived cells can be scaled up for high-throughput assays and drug screening based on phenotypic rescue, eventually contributing to therapeutics, cell replacement, and precision medicine for the patient.