This system also provides a platform on which, together with deep and superficial cortical neurons, human astrocytes are generated from an identical genetic background. Astrocytes powerfully control synapse formation and function and are critical for proper neural development35,36. In contrast to existing protocols for generating astrocytes from hiPSCs or by direct conversion37,38, here the astrocytes dispersed throughout the hCS develop spontaneously without the need for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) or serum, which are known activators of astrocytes. It is likely that the generation and close spatial integration of astrocytes inside hCSs mediate synaptogenic mechanisms that ultimately produce robust synaptic responses39,40. In fact, neurons in the hCS are more transcription-ally and electrophysiologically mature than neurons generated through conventional methods.
