To obtain target cells with high purity on a large scale, purification and enrichment technologies using specific cell surface markers121,122, cell-specific promoters123 and microRNAs124 have been established. In the first report of large-scale drug screening using an iPSC-based disease model, neural crest precursors for autonomic neurons were sorted and purified from iPSCs derived from patients with familial dysautonomia, a monogenic early-onset disease that is characterized by degeneration of neurons in the sensory and autonomic nervous systems121. It is caused by mutations in the gene coding for the IkB kinase complex-associated protein (IKBKAP) that result in a splicing defect and production of a dysfunctional truncated protein. The screening was conducted using 6,912 compounds, and a compound known as SKF-86466 was found to improve disease-specific aberrant splicing. Interestingly, SKF-86466 was not effective in non-target cells, including iPSCs, fibroblasts, and lymphocytes. These results illustrated the advantage of iPSC-based drug screening to explore cell type-specific pathogenesis.
