Seeing a specific phenotype in disease-relevant neurons in vitro represents an exciting first step in the development of an iPSC-based disease model. However, it is often challenging to determine the significance of an in vitro phenotype for a given disease. Such phenotypes are difficult to evaluate given the lack of primary tissue from patients for further confirmation and the overall lack of understanding of disease-initiating events in neuropsychiatric diseases. One desirable endpoint is to use such disease-related phenotypes as the starting point for HTS, which allows for testing hundreds of compounds simultaneously. One group has developed a HTS for testing various compounds on human iPSC-derived neurons for modulators of the Wnt/GSK3β signaling system,66 a system further validated through the use of lithium.
