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Nature. 2017 May 4;545(7652):48-53. doi: 10.1038/nature22047. Epub 2017 Apr 26.

Cell diversity and network dynamics in photosensitive human brain organoids.

Author information

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Department of Cellular and Molecular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
Departments of Biological Engineering and Brain and Cognitive Sciences, MIT Media Lab and McGovern Institute, MIT, Cambridge, Massachusetts 02139, USA.
LeafLabs, LLC, Cambridge, Massachusetts 02139, USA.
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.


In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.

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