Fig. 4

Investigation of NDDs using human iPSCs and proteomics. (a) Biological samples from affected and unaffected individuals can be reprogrammed into iPSCs, which can be genetically edited to correct potential disease-relevant mutations or introduce gene disruptions and/or patient mutations. These iPSCs can then be differentiated into multiple cell types including neurons and then compared at the cellular and proteome levels. (b) The use of human iPSCs allows for the investigation of the proteome at different time points during development, including the iPSC stage, the neural progenitor stage, and the fully differentiated stage. Neuronal and glial 2D cell cultures can be studied, as well as 3D neural organoids that mimic human brain development. Proteomics with iPSC-derived neurons provides the potential to identify human PTM programs (c), human disease biomarkers (d), and human PINs (e)