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Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes.

TitleSystematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes.
Publication TypeJournal Article
Year of Publication2017
AuthorsKrencik R, Seo K, van Asperen JV, Basu N, Cvetkovic C, Barlas S, Chen R, Ludwig C, Wang C, Ward ME, Gan L, Horner PJ, Rowitch DH, Ullian EM
JournalStem Cell Reports
Volume9
Issue6
Pagination1745-1753
Date Published2017 12 12
ISSN2213-6711
KeywordsAstrocytes, Cell Differentiation, Cell Lineage, Cells, Cultured, Coculture Techniques, Humans, Neural Stem Cells, Neurons, Pluripotent Stem Cells, Synapses
Abstract

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.

DOI10.1016/j.stemcr.2017.10.026
Alternate JournalStem Cell Reports
PubMed ID29198827
PubMed Central IDPMC5785708
Grant ListMC_PC_12009 / / Medical Research Council / United Kingdom
P30 EY002162 / EY / NEI NIH HHS / United States
R01 MH099595 / MH / NIMH NIH HHS / United States