Astrocytic cell adhesion genes linked to schizophrenia correlate with synaptic programs in neurons
Olli Pietiläinen, Aditi Trehan, Daniel Meyer, Jana M. Mitchell, Matthew Tegtmeyer, Vera Valakh, Hilena Gebre, Theresa Chen, Emilia Vartiainen, Samouil L. Farhi, Kevin Eggan, Steven A. McCarroll, Ralda Nehme
Abstract
The maturation of neurons and the development of synapses, although emblematic of neurons, also relies on interactions with astrocytes and other glia. Here, to study the role of glia-neuron interactions, we analyze the transcriptomes of human pluripotent stem cell (hPSC)-derived neurons, from 80 human donors, that were cultured with or without contact with glial cells. We find that the presence of astrocytes enhances synaptic gene-expression programs in neurons when in physical contact with astrocytes. These changes in neurons correlate with increased expression, in the cocultured glia, of genes that encode synaptic cell adhesion molecules. Both the neuronal and astrocyte gene-expression programs are enriched for genes associated with schizophrenia risk. Our results suggest that astrocyte-expressed genes with synaptic functions are associated with stronger expression of synaptic genetic programs in neurons, and they suggest a potential role for astrocyte-neuron interactions in schizophrenia.