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

Hedegaard, Anne, Monzón-Sandoval, Jimena, Newey, Sarah E., Whiteley, Emma S., Webber, Caleb and Akerman, Colin J. 2020. Pro-maturational effects of human iPSC-derived cortical astrocytes upon iPSC-derived cortical neurons. Stem Cell Reports 15 , pp. 1-14. 10.1016/j.stemcr.2020.05.003

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Abstract

Astrocytes influence neuronal maturation and function by providing trophic support, regulating the extracellular environment, andmodulating signaling at synapses. The emergence of induced pluripotent stem cell (iPSC) technology offers a human system with whichto validate and re-evaluate insights from animal studies. Here, we set out to examine interactions between human astrocytes and neuronsderived from a common cortical progenitor pool, thereby recapitulating aspects ofin vivocortical development. We show that the corticaliPSC-derived astrocytesexhibit many of the molecular and functional hallmarks of astrocytes. Furthermore, optogenetic and electrophys-iological co-culture experiments reveal that the iPSC-astrocytes can actively modulate ongoing synaptic transmission and exertpro-maturational effects upon developing networks of iPSC-derived cortical neurons. Finally, transcriptomic analyses implicate syn-apse-associated extracellular signaling in the astrocytes’ pro-maturational effects upon the iPSC-derived neurons. This work helps laythe foundation for future investigations into astrocyte-to-neuron interactions in human health and disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	2213-6711
Date of First Compliant Deposit:	23 June 2020
Date of Acceptance:	4 May 2020
Last Modified:	31 Jul 2020 16:14
URI:	http://orca-mwe.cf.ac.uk/id/eprint/132690

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