The rise of three-dimensional human brain cultures

Abstract

Pluripotent stem cells show a remarkable ability to self-organize and differentiate in vitro in three-dimensional aggregates, known as organoids or organ spheroids, and to recapitulate aspects of human brain development and function. Region-specific 3D brain cultures can be derived from any individual and assembled to model complex cell–cell interactions and to generate circuits in human brain assembloids. Here I discuss how this approach can be used to understand unique features of the human brain and to gain insights into neuropsychiatric disorders. In addition, I consider the challenges faced by researchers in further improving and developing methods to probe and manipulate patient-derived 3D brain cultures.

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Figure 1: Self-organization and organogenesis.
Figure 2: Different approaches for deriving human brain 3D cultures.
Figure 3: Human brain assembloids.
Figure 4: Methods for probing 3D brain assembloids.

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Acknowledgements

The author thanks B. A. Barres, K. Deisseroth, R. Reimer, J. A. Bernstein, H. B. Fraser, J. R. Huguenard and members of the Pasca laboratory, and acknowledges funding support from the National Institute of Mental Health (NIMH), California Institute of Regenerative Medicine (CIRM), the MQ Fellow Award, the Donald E. and Delia B. Baxter Foundation Award, the Stanford Neurosciences Institute’s Brain Rejuvenation Project, the Kwan Research Fund and the Brain & Behavior Research Foundation (BBRF, NARSAD).

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Correspondence to Sergiu P. Pașca.

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Pașca, S. The rise of three-dimensional human brain cultures. Nature 553, 437–445 (2018). https://doi.org/10.1038/nature25032

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