Organ-Chips Enhance the Maturation of Human iPSC-Derived Dopamine Neurons
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PROVIDER: S-EPMC10531789 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:Organ-Chips Enhance the Maturation of Human iPSC-Derived Dopamine Neurons
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Project description:We show neural enhancement and induction of vascular interaction genes in iPSC-derived spinal motor neurons that have been incubated in a microengineered chip.
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Project description: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.
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