摘要:SummaryAlthough astrocytes are involved in the pathogenesis of CNS diseases, how they induce synaptic abnormalities is unclear. Currently,in vitropathological astrocyte cultures or animal models do not reproduce human disease phenotypes accurately. Induced pluripotent stem cells (iPSCs) are replacing animal models in pathological studies. We developed an autaptic culture (AC) system containing single neuron cultures grown on microislands of astrocytes. AC with human iPSC-derived astrocytes (HiA) was established. We evaluated the effect of astrocytes on the synaptic functions of human-derived neurons. We found a significantly higher Na+current amplitude, membrane capacitance, and number of synapses, as well as longer dendrites, in HiAACs compared with neuron monocultures. Furthermore, HiAs were involved in the formation and maturation of functional synapses that exhibited excitatory postsynaptic currents. This system can facilitate the study of CNS diseases and advance the development of drugs targeting glial cells.Graphical abstractDisplay OmittedHighlights•We developed an autaptic culture with human iPSCs-derived astrocytes•Neurons in HiAACs developed after culture and formed functional synapses•EPSC and mEPSC were recorded showing HiAs promoted synapse formation/maturation•Autaptic cultures can be used to analyze synaptic activity and human CNS diseaseBiological sciences; Neuroscience; Cellular neuroscience; Cell biology; Stem cells research