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Cell diversity and network dynamics in photosensitive human brain organoids

Giorgia Quadrato (), Tuan Nguyen, Evan Z. Macosko, John L. Sherwood, Sung Min Yang, Daniel R. Berger, Natalie Maria, Jorg Scholvin, Melissa Goldman, Justin P. Kinney, Edward S. Boyden, Jeff W. Lichtman, Ziv M. Williams, Steven A. McCarroll and Paola Arlotta ()
Additional contact information
Giorgia Quadrato: Harvard University
Tuan Nguyen: Harvard University
Evan Z. Macosko: Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT
John L. Sherwood: Harvard University
Sung Min Yang: Harvard University
Daniel R. Berger: Harvard University
Natalie Maria: Harvard University
Jorg Scholvin: MIT Media Lab and McGovern Institute, MIT
Melissa Goldman: Harvard Medical School
Justin P. Kinney: LeafLabs, LLC
Edward S. Boyden: MIT Media Lab and McGovern Institute, MIT
Jeff W. Lichtman: Harvard University
Ziv M. Williams: Massachusetts General Hospital, Harvard Medical School
Steven A. McCarroll: Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT
Paola Arlotta: Harvard University

Nature, 2017, vol. 545, issue 7652, 48-53

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/nature22047

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