From a medical point of view, direct lineage reprogramming provides an alternative potentially complementary tool to many of the proposed applications of iPS cell technology for both disease modeling and development of cell-based therapies. Recently, several elegant reports of assessing disease-related phenotypes in iPS cell-derived neurons have provided an important proof-of-principle that at least some cellular aspects of complex brain diseases can be recapitulated with patient-derived cells in vitro (Marchetto et al., 2010, Brennand et al., 2011, Nguyen et al., 2011). Both iPS and iN cell approaches are complicated by the heterogeneity with respect to maturation and presumably subtype specification. Especially iPS cells have shown a substantial line-to-line variability with regards to differentiation potential (Hu et al., 2010). Future studies will show whether directly generated iN cells can provide a better representation of the cellular variability, which might in turn simplify the discovery and analysis of disease-associated phenotypes. Moreover, the generation of iN cells from a large cohort of patients appears quite feasible whereas the generation and neuronal differentiation of iPS cells would be a very cumbersome and slow process.
