Generation of Cortical, Dopaminergic, Motor, and Sensory Neurons from Human Pluripotent Stem Cells

The use of patient-derived induced pluripotent stem cells (iPSCs) and their neural derivatives is becoming increasingly important in the study of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, peripheral neuropathy, and so on. Increasingly, iPSC-derived neurons also reveal key pathways and signaling defects in psychiatric disorders such as autism spectrum disorders, schizophrenia, and bipolar disorder. With recent advances in CRISPR/Cas9-mediated genome editing technology, patient-derived iPSCs with disease-causing mutations can be corrected into "isogenic control lines," and these can be differentiated into neural derivatives with identical genetic background. This provides an opportunity for in vitro disease modeling to unravel disease mechanisms and a platform to facilitate drug discovery. In this chapter, we provide details of the differentiation protocols to reliably derive four currently relevant neuronal subtypes, i.e., cortical neurons, midbrain dopaminergic neurons, spinal motor neurons, and sensory neurons.