Protocol for morphogen-guided differentiation of brain cell types using human induced pluripotent stem cells.

Modeling neurological disorders is challenging due to differing functional genomics and phenotypes among species. Here, we present a protocol for morphogen-guided differentiation of human induced pluripotent stem cells (hiPSCs) into microglia, astrocytes, and mixed cortical cultures (MCCs) for studying human brain disorders. We describe steps for enhancing microglial production using hypoxia and implementing quality-control measures for astrocyte and MCC differentiations. We detail knockout serum replacement procedures for serum-free astrocytes. This protocol enables cell-type-specific investigation of disease mechanisms and drug screening.