title: Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.
abstract: Cerebral organoids-3D cultures of human cerebral tissue derived from pluripotent stem cells-have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, 04103 Leipzig, Germany;
authors.forename: J Gray
authors.initials: JG
authors.lastname: Camp
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
authors.forename: Farhath
authors.initials: F
authors.lastname: Badsha
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
authors.forename: Marta
authors.initials: M
authors.lastname: Florio
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, 04103 Leipzig, Germany;
authors.forename: Sabina
authors.initials: S
authors.lastname: Kanton
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, 04103 Leipzig, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Gerber
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
authors.forename: Michaela
authors.initials: M
authors.lastname: Wilsch-Bräuninger
authors.affiliation: Institut de Biologie, Ecole Normale Superieure, 75005 Paris, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Lewitus
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
authors.forename: Alex
authors.initials: A
authors.lastname: Sykes
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, 04103 Leipzig, Germany;
authors.forename: Wulf
authors.initials: W
authors.lastname: Hevers
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria;
authors.forename: Madeline
authors.initials: M
authors.lastname: Lancaster
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria;
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
authors.affiliation: Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, 01307 Dresden, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Lachmann
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, 04103 Leipzig, Germany; barbara_treutlein@eva.mpg.de paabo@eva.mpg.de huttner@mpi-cbg.de.
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; barbara_treutlein@eva.mpg.de paabo@eva.mpg.de huttner@mpi-cbg.de.
authors.forename: Wieland B
authors.initials: WB
authors.lastname: Huttner
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, 04103 Leipzig, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; barbara_treutlein@eva.mpg.de paabo@eva.mpg.de huttner@mpi-cbg.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Treutlein
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D019579:Neocortex / Q000196:embryology*; D009940:Organoids / Q000502:physiology*; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D046509:Tissue Culture Techniques
keywords: cerebral organoid; corticogenesis; neocortex; single-cell RNA-seq; stem cells