The models described above exploit the ability of hiPSCs to be differentiated into neurons while retaining the unique genetic signature of the individual from whom they were derived, thereby replicating the developmental trajectory of an individual’s brain development on the basis of their genetic code. So-called microenvironmental effects can also be studied in hiPSC-based organoid systems; these effects include cell-to-cell interactions, the effects of age and the effects of diffusible substances generated by developing cells; it is well known that the transcriptome and epigenome are dynamically altered by the cellular micro-environment. However, hiPSCs by themselves offer little to no insight into the macro-environmental component of the pathogenesis of neurodevelopmental disorders, such as organism-level effects and interactions (for example, hormones and sensory experiences). HiPSC organoid systems could, therefore, be exposed to toxic chemicals or immune challenges that mimic detrimental environmental effects to study the consequences on development.
