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

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

Research output: Contribution to journalArticle

25 Scopus citations

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.

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

Keywords

  • astrocytes
  • coculture
  • disease modeling
  • human pluripotent stem cells
  • neurons
  • organoids
  • synapses
  • three-dimensional spheres

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes'. Together they form a unique fingerprint.

Cite this