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

Research output: Contribution to journalArticle

Robert Krencik, Kyounghee Seo, Jessy V. van Asperen, Nupur Basu, Caroline Cvetkovic, Saba Barlas, Robert Chen, Connor Ludwig, Chao Wang, Michael E. Ward, Li Gan, Philip J. Horner, David H. Rowitch, Erik M. Ullian

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.

Original languageEnglish (US)
Pages (from-to)1745-1753
Number of pages9
JournalStem Cell Reports
Volume9
Issue number6
Early online dateNov 30 2017
DOIs
StatePublished - Dec 12 2017

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Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes. / Krencik, Robert; Seo, Kyounghee; van Asperen, Jessy V.; Basu, Nupur; Cvetkovic, Caroline; Barlas, Saba; Chen, Robert; Ludwig, Connor; Wang, Chao; Ward, Michael E.; Gan, Li; Horner, Philip J.; Rowitch, David H.; Ullian, Erik M.

In: Stem Cell Reports, Vol. 9, No. 6, 12.12.2017, p. 1745-1753.

Research output: Contribution to journalArticle

Harvard

Krencik, 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 2017, 'Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes' Stem Cell Reports, vol. 9, no. 6, pp. 1745-1753. https://doi.org/10.1016/j.stemcr.2017.10.026

APA

Krencik, R., Seo, K., van Asperen, J. V., Basu, N., Cvetkovic, C., Barlas, S., ... Ullian, E. M. (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

Vancouver

Krencik R, Seo K, van Asperen JV, Basu N, Cvetkovic C, Barlas S et al. Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes. Stem Cell Reports. 2017 Dec 12;9(6):1745-1753. https://doi.org/10.1016/j.stemcr.2017.10.026

Author

Krencik, Robert ; Seo, Kyounghee ; van Asperen, Jessy V. ; Basu, Nupur ; Cvetkovic, Caroline ; Barlas, Saba ; Chen, Robert ; Ludwig, Connor ; Wang, Chao ; Ward, Michael E. ; Gan, Li ; Horner, Philip J. ; Rowitch, David H. ; Ullian, Erik M. / Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes. In: Stem Cell Reports. 2017 ; Vol. 9, No. 6. pp. 1745-1753.

BibTeX

@article{c7e7d49bb16048ffbb024734c00029ff,
title = "Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes",
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. 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.",
keywords = "astrocytes, coculture, disease modeling, human pluripotent stem cells, neurons, organoids, synapses, three-dimensional spheres",
author = "Robert Krencik and Kyounghee Seo and {van Asperen}, {Jessy V.} and Nupur Basu and Caroline Cvetkovic and Saba Barlas and Robert Chen and Connor Ludwig and Chao Wang and Ward, {Michael E.} and Li Gan and Horner, {Philip J.} and Rowitch, {David H.} and Ullian, {Erik M.}",
year = "2017",
month = "12",
day = "12",
doi = "10.1016/j.stemcr.2017.10.026",
language = "English (US)",
volume = "9",
pages = "1745--1753",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Elsevier",
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RIS

TY - JOUR

T1 - Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes

AU - Krencik, Robert

AU - Seo, Kyounghee

AU - van Asperen, Jessy V.

AU - Basu, Nupur

AU - Cvetkovic, Caroline

AU - Barlas, Saba

AU - Chen, Robert

AU - Ludwig, Connor

AU - Wang, Chao

AU - Ward, Michael E.

AU - Gan, Li

AU - Horner, Philip J.

AU - Rowitch, David H.

AU - Ullian, Erik M.

PY - 2017/12/12

Y1 - 2017/12/12

N2 - 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.

AB - 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.

KW - astrocytes

KW - coculture

KW - disease modeling

KW - human pluripotent stem cells

KW - neurons

KW - organoids

KW - synapses

KW - three-dimensional spheres

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U2 - 10.1016/j.stemcr.2017.10.026

DO - 10.1016/j.stemcr.2017.10.026

M3 - Article

VL - 9

SP - 1745

EP - 1753

JO - Stem Cell Reports

T2 - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 6

ER -

ID: 37462619