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

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. [Display omitted] •Systematic comparison to uncover unique features in each brain organoid protocol•Similar cell compositions across protocols•Distinct preference of differentiation trajectories across protocols•Generation of interneurons from human cortical organoids Tanaka et al. report integrative analyses of single-cell RNA-seq for human brain organoids derived from different protocols. They find a unique preference of cell differentiation routes across protocols and provide a benchmark for the use and the improvement of human brain organoids.