Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes
van Asperen, JV
Stem Cell Reports
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Krencik, R., Seo, K., van Asperen, J., Basu, N., Cvetkovic, C., Barlas, S., Chen, R., et al. (2017). Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes. Stem Cell Reports, 9 (6), 1745-1753. https://doi.org/10.1016/j.stemcr.2017.10.026
© 2017 The Authors Human astrocytes network with neurons in dynamic ways that are still poorly defined. Our ability to model this relationship is hampered by the lack of relevant and convenient tools to recapitulate this complex interaction. To address this barrier, we have devised efficient coculture systems utilizing 3D organoid-like spheres, termed asteroids, containing pre-differentiated human pluripotent stem cell (hPSC)-derived astrocytes (hAstros) combined with neurons generated from hPSC-derived neural stem cells (hNeurons) or directly induced via Neurogenin 2 overexpression (iNeurons). Our systematic methods rapidly produce structurally complex hAstros and synapses in high-density coculture with iNeurons in precise numbers, allowing for improved studies of neural circuit function, disease modeling, and drug screening. We conclude that these bioengineered neural circuit model systems are reliable and scalable tools to accurately study aspects of human astrocyte-neuron functional properties while being easily accessible for cell-type-specific manipulations and observations. In this article, Krencik and colleagues show that high-density cocultures of pre-differentiated human astrocytes with induced neurons, from pluripotent stem cells, elicit mature characteristics by 3–5 weeks. This provides a faster and more defined alternative method to organoid cultures for investigating human neural circuit function.
This work has been supported by the Paul G. Allen Family Foundation Award, SFARI Award 345471, NIMH ( R01MH099595-01 ), That Man May See, NIH-NEI ( EY002162 ) Core Grant for Vision Research, and the Research to Prevent Blindness Unrestricted Grant.
External DOI: https://doi.org/10.1016/j.stemcr.2017.10.026
This record's URL: https://www.repository.cam.ac.uk/handle/1810/274339
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Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
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