Fig. 1

Modeling the nigrostriatal niche. Schematic representation of nigrostriatal multilineage co-culture models. a Human pluripotent stem cells (hPSC) undergo specific protocols of differentiation and generate region-patterned organoids (midbrain in yellow; forebrain in blue), as well as microglia (green). b Organoids dissociation allows for the isolation of neuronal populations and patterned astrocytes for further analysis. Dopaminergic neurons rise from the midbrain organoid (DNs, yellow), medium spiny neurons from the forebrain organoid (MSNs, blue), and region-patterned astrocytes from either one (purple). c hPSC-derived components are engineered into co-culture models. Midbrain and forebrain organoids are assembled and integrated with microglia to generate a multilineage assembloids model, which allows for neuronal circuit formation and neuro-immune communication in a 3D environment. Dissociated components are combined in 2D co-culture, a model in which each component can undergo differential genomic editing