Fig. 2
Principals of patient stratification for subsequent human-induced pluripotent stem cell (hiPSC-)-based cellular disease modelling combining genetics, white matter pathology and cognitive impairments. a Subsets of SCZ risk genes (as indicated by the red part of the DNA symbol) impair cognitive performance. Red human icons illustrate such risk gene carriers. Recent evidence suggests that the effect of these ‘cognitive’ risk genes is at least in part connected to white matter pathology. Sufficient patient stratification is needed to reveal the underlining mechanisms of white matter pathology. Clinical deep phenotyping, with a focus on neurocognitive testing, combined with imaging of white matter is probably a suitable approach to identify the corresponding subgroup of patients. Additional stratification based on cell-specific PRSs might further increase stratification precision. b hiPSC technology enables the generation of a toolbox of patient-derived cell systems. Monocultures of glial cells and neurons and myelinating co-culture systems may simulate disease-relevant aspects of SCZ in 2D and 3D cellular systems in vitro. Moreover, hiPSC-derived cells can be tested in chimeric mouse models in vivo. NB: The illustrations of the ‘chimeric mouse’ and the DNA ‘risk alleles’ have been published previously100
