학술논문
Multiscale 3D phenotyping of human cerebral organoids.
Document Type
Academic Journal
Author
Albanese A; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.; Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.; Swaney JM; Department of Chemical Engineering, MIT, Cambridge, MA, USA.; Yun DH; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.; Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.; Evans NB; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.; Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.; Antonucci JM; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.; Velasco S; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Sohn CH; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.; Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.; Arlotta P; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Gehrke L; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA.; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, 02139, USA.; Chung K; Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA. khchung@mit.edu.; Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA. khchung@mit.edu.; Department of Chemical Engineering, MIT, Cambridge, MA, USA. khchung@mit.edu.; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA. khchung@mit.edu.; Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, Republic of Korea. khchung@mit.edu.; Yonsei-IBS Institute, Yonsei University, Seoul, Republic of Korea. khchung@mit.edu.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Subject
Language
English
Abstract
Brain organoids grown from human pluripotent stem cells self-organize into cytoarchitectures resembling the developing human brain. These three-dimensional models offer an unprecedented opportunity to study human brain development and dysfunction. Characterization currently sacrifices spatial information for single-cell or histological analysis leaving whole-tissue analysis mostly unexplored. Here, we present the SCOUT pipeline for automated multiscale comparative analysis of intact cerebral organoids. Our integrated technology platform can rapidly clear, label, and image intact organoids. Algorithmic- and convolutional neural network-based image analysis extract hundreds of features characterizing molecular, cellular, spatial, cytoarchitectural, and organoid-wide properties from fluorescence microscopy datasets. Comprehensive analysis of 46 intact organoids and ~ 100 million cells reveals quantitative multiscale "phenotypes" for organoid development, culture protocols and Zika virus infection. SCOUT provides a much-needed framework for comparative analysis of emerging 3D in vitro models using fluorescence microscopy.