Pro-maturational Effects of Human iPSC-Derived Cortical Astrocytes upon iPSC-Derived Cortical Neurons

• Published in: Stem cell reports 2020-07, Vol.15 (1), p.38-51
• Main Authors: Hedegaard, Anne, Monzón-Sandoval, Jimena, Newey, Sarah E., Whiteley, Emma S., Webber, Caleb, Akerman, Colin J.
• Format: Article
• Language: English
• Subjects: astrocyte-neuron interactions; astrocytes; co-culture; gliotransmission; induced pluripotent stem cells; optogenetics; synaptic maturation
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2020.05.003

Astrocytes influence neuronal maturation and function by providing trophic support, regulating the extracellular environment, and modulating signaling at synapses. The emergence of induced pluripotent stem cell (iPSC) technology offers a human system with which to validate and re-evaluate insights from animal studies. Here, we set out to examine interactions between human astrocytes and neurons derived from a common cortical progenitor pool, thereby recapitulating aspects of in vivo cortical development. We show that the cortical iPSC-derived astrocytes exhibit many of the molecular and functional hallmarks of astrocytes. Furthermore, optogenetic and electrophysiological co-culture experiments reveal that the iPSC-astrocytes can actively modulate ongoing synaptic transmission and exert pro-maturational effects upon developing networks of iPSC-derived cortical neurons. Finally, transcriptomic analyses implicate synapse-associated extracellular signaling in the astrocytes' pro-maturational effects upon the iPSC-derived neurons. This work helps lay the foundation for future investigations into astrocyte-to-neuron interactions in human health and disease. [Display omitted] •Human astrocytes and neurons are generated from a common cortical progenitor pool•Astrocyte-neuron signaling is demonstrated with neurotransmitters and optogenetics•Astrocyte co-culture promotes cortical neuron and synaptic network maturation•Transcriptomics reveal extracellular astrocytic proteins that interact at synapses In this article, Akerman and colleagues provide a molecular and functional characterization of human iPSC-derived cortical astrocytes. The astrocytes can modulate ongoing excitatory synaptic transmission between iPSC-derived cortical neurons. When co-cultured, the astrocytes enhance the functional maturation of cortical synaptic networks. Finally, transcriptomic analyses indicate that the astrocytes engage in synapse-associated extracellular signaling to mediate their pro-maturational effects.