Lastly, variability in hiPSC derived neurons even amongst control subjects can be a concern for disease modeling (Choi et al., 2015; Kilpinen et al., 2017; Kyttälä et al., 2016). For example, a recent study exhaustively characterized differentiation capacity, cellular morphology, and copy number alterations through genome wide profiling of 711 hiPSC lines from 301 healthy individuals revealing that most variation results from differences between individuals (Kilpinen et al., 2017). Designing a hiPSC study with sufficient statistical power would require large samples sizes, which is impractical both in terms of cost and lack of techniques for high-throughput functional analyses. However, implementation of genetically-engineered hiPSCs can provide a reasonable solution to this limitation (see above).
