Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons

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 f...

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Main Authors: Anne Hedegaard, Jimena Monzón-Sandoval, Sarah E Newey, Emma S Whiteley, Caleb Webber, Colin J Akerman
Format: Journal article
Language:English
Published: Cell Press 2020
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author Anne Hedegaard
Jimena Monzón-Sandoval
Sarah E Newey
Emma S Whiteley
Caleb Webber
Colin J Akerman
author_facet Anne Hedegaard
Jimena Monzón-Sandoval
Sarah E Newey
Emma S Whiteley
Caleb Webber
Colin J Akerman
author_sort Anne Hedegaard
collection OXFORD
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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spelling oxford-uuid:cb8f381e-97ed-4e69-8196-18f7f51f99db2022-03-27T07:15:45ZPro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neuronsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cb8f381e-97ed-4e69-8196-18f7f51f99dbEnglishSymplectic ElementsCell Press2020Anne HedegaardJimena Monzón-SandovalSarah E NeweyEmma S WhiteleyCaleb WebberColin J AkermanAstrocytes 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.
spellingShingle Anne Hedegaard
Jimena Monzón-Sandoval
Sarah E Newey
Emma S Whiteley
Caleb Webber
Colin J Akerman
Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons
title Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons
title_full Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons
title_fullStr Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons
title_full_unstemmed Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons
title_short Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons
title_sort pro maturational effects of human ipsc derived cortical astrocytes upon ipsc derived cortical neurons
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AT jimenamonzonsandoval promaturationaleffectsofhumanipscderivedcorticalastrocytesuponipscderivedcorticalneurons
AT sarahenewey promaturationaleffectsofhumanipscderivedcorticalastrocytesuponipscderivedcorticalneurons
AT emmaswhiteley promaturationaleffectsofhumanipscderivedcorticalastrocytesuponipscderivedcorticalneurons
AT calebwebber promaturationaleffectsofhumanipscderivedcorticalastrocytesuponipscderivedcorticalneurons
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