Lorenz Studer, from Memorial Sloan-Kettering Cancer Center, described work modeling two rare human diseases, familial dysautonomia (FD) and Hirschsprung’s disease (colonic aganglionosis). FD is a rare recessive disorder, occurring when a T → C point mutation leads to skipping of exon 20 in iKBKAP/ELP1. Deriving hiPSCs from patients with both severe (S1 and S2) and mild (M1 and M2) FD, he found that patient-derived hiPSC neurons clearly modeled clinical outcome; relative to unaffected controls, severe FD patients had difficulty generating BRN3A sensory neurons, whereas mild FD patients did not (sensory neurons from both classes of patients die within 28 days). To study Hirschsprung’s disease, a fatal if untreated disease in which there is incomplete migration of the enteric nervous system, Studer described a differentiation protocol that successfully generates vagal and enteric neural crest from hESCs that express appropriate cell-type-specific BRN3A/ISL1 markers, produce slow wave activity in vitro, and properly innervate the colon when transplanted into mice (Chambers et al., 2013). hESC-derived ENRB−/− and RET−/− enteric neural crest cells showed reduced migration in vitro and in vivo. A high-throughput screening (HTS)
