Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
- PMID: 26005811
- PMCID: PMC4489980
- DOI: 10.1038/nmeth.3415
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Abstract
The human cerebral cortex develops through an elaborate succession of cellular events that, when disrupted, can lead to neuropsychiatric disease. The ability to reprogram somatic cells into pluripotent cells that can be differentiated in vitro provides a unique opportunity to study normal and abnormal corticogenesis. Here, we present a simple and reproducible 3D culture approach for generating a laminated cerebral cortex-like structure, named human cortical spheroids (hCSs), from pluripotent stem cells. hCSs contain neurons from both deep and superficial cortical layers and map transcriptionally to in vivo fetal development. These neurons are electrophysiologically mature, display spontaneous activity, are surrounded by nonreactive astrocytes and form functional synapses. Experiments in acute hCS slices demonstrate that cortical neurons participate in network activity and produce complex synaptic events. These 3D cultures should allow a detailed interrogation of human cortical development, function and disease, and may prove a versatile platform for generating other neuronal and glial subtypes in vitro.
Conflict of interest statement
The authors declare no competing financial interests.
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- Paşca SP, Panagiotakos G, Dolmetsch RE. Generating human neurons in vitro and using them to understand neuropsychiatric disease. Annu Rev Neurosci. 2014;37:479–501. - PubMed
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