Table 1 |.

Comparison of main organoid generation approaches

Reference	Format	Variability	Applications	Considerations/uniqueness
Eiraku et al.5	Guided	Low	Genetic disease, drug dosing, drug screening	Low variability is attractive for drug screening; development and metabolomics may be influenced by presence of insulin in some protocols; may not have spontaneous inhibitory neuron development49
Lancaster et al.19	Unguided	High	Lissencephalies, genetic disease, whole brain development	Spontaneous development of multiple brain regions; high cell diversity, high organoid to organoid variability. Newer adaptations can produce neural oscillations21
Trujillo et al.7	Guided or ‘semi-guided’	Medium (Extended Data Fig. 2)	Genetic disease, metabolic disease, population level spontaneous electrical activity, drug dosing/screening	Spontaneous emergence of physiologically relevant oscillatory activity from functional excitatory–inhibitory neuron development; expected tradeoff of efficiency/variability due to semi-guided nature, long-term developmental scale. Can be used only to model cortical-born interneurons, not ganglionic eminence-born interneurons or migration of interneurons to the cortex. Resultant organoids follow the neurodevelopment of the human brain