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Cell Rep. 2020 Feb 11;30(6):1682-1689.e3. doi: 10.1016/j.celrep.2020.01.038.

Synthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain.

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Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Pediatric Research, Oslo University Hospital and University of Oslo, PO Box 1112 Blindern, 0317 Oslo, Norway.
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address:


Human brain organoid systems offer unprecedented opportunities to investigate both neurodevelopmental and neurological disease. Single-cell-based transcriptomics or epigenomics have dissected the cellular and molecular heterogeneity in the brain organoids, revealing a complex organization. Similar but distinct protocols from different labs have been applied to generate brain organoids, providing a large resource to perform a comparative analysis of brain developmental processes. Here, we take a systematic approach to compare the single-cell transcriptomes of various human cortical brain organoids together with fetal brain to define the identity of specific cell types and differentiation routes in each method. Importantly, we identify unique developmental programs in each protocol compared to fetal brain, which will be a critical benchmark for the utility of human brain organoids in the future.


brain development; brain organoid; cortical spheroids; developmental trajectory; hCOs; hESC; protocol comparison; scRNA-seq; stem cells

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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