Stem Cell Reports
Volume 15, Issue 1, 14 July 2020, Pages 38-51
Journal home page for Stem Cell Reports

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

https://doi.org/10.1016/j.stemcr.2020.05.003Get rights and content
Under a Creative Commons license
open access

Highlights

  • 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

Summary

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.

Keywords

induced pluripotent stem cells
astrocytes
co-culture
synaptic maturation
astrocyte-neuron interactions
optogenetics
gliotransmission

Cited by (0)