It is increasingly clear that somatic mosaicism occurs in both post-mortem and hiPSC neurons. What remains to be determined is the precise extent of this phenomenon in the human brain, its mechanisms, and the precise role that mosaicism contributes to evolution, human behavior and disease, and even the “normal” physiological condition. Moving forward, future hiPSC experiments should be designed with a consideration of the existence of somatic mosaicism, incorporating (1) analysis of multiple iPSC lines per patient, (2) isogenic engineering, and (3) phenotypic rescue experiments.
