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Nat Methods. 2015 Jul;12(7):671-8. doi: 10.1038/nmeth.3415. Epub 2015 May 25.

Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.

Author information

1
Department of Pediatrics, Division of Neonatology, Stanford University School of Medicine, Stanford, California, USA.
2
Department of Neurobiology, Stanford University School of Medicine, Stanford, California, USA.
3
1] Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [3] Interdepartmental Ph.D. Program in Bioinformatics, University of California, Los Angeles, California, USA.
4
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
5
Department of Psychiatry &Behavioral Sciences, Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, California, USA.
6
1] Department of Pharmacology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. [2] BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
7
Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine, Stanford, California, USA.
8
Department of Pathology, Blood Center, Stanford University School of Medicine, Stanford, California, USA.
9
1] Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine, Stanford, California, USA. [2] Department of Synapse Biology, Allen Institute for Brain Science, Seattle, Washington, USA.

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.

PMID:
26005811
PMCID:
PMC4489980
DOI:
10.1038/nmeth.3415
[Indexed for MEDLINE]
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