memory is retained through the reprogramming process, which is supported by the tendency of iPSCs derived from blood cells to preferentially differentiate toward mesoderm lineages (that is, their lineage of origin).28 However, such epigenetic memory may not persist long-term in iPSCs as repeated passaging at the pluripotent state is correlated with a loss of the lineage-specific differentiation bias.92 Furthermore, there is a possibility that some retained epigenetic memory represents incomplete reprogramming of the iPSCs. Transdifferentiated cells (iNs) appear to retain much of their original epigenetic landscape.93 Thus, generating iNs could be a valid alternative for the modeling of environmentally induced neuropsychiatric diseases. Although induced neuron technology may better preserve the epigenetic landscape of the patient donor cell, epigenetic modifications vary across different cell types and therefore changes in skin fibroblasts may not capture important neuron-specific disease-related epigenetic differences.94 The emerging field of transgenerational epigenetic inheritance provides evidence that environmental influences, including nutrition or stress, can modify epigenetic marks inherited across the germline.95, 96 Thus, such marks may persist through the reprogramming process and be of use in the study of mental illness with environmental contributions.
