title: Self-organized developmental patterning and differentiation in cerebral organoids.
abstract: Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso-ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulatedin vitro.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Renner
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria.|MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Madeline A
authors.initials: MA
authors.lastname: Lancaster
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Shan
authors.initials: S
authors.lastname: Bian
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
authors.forename: Heejin
authors.identifier: 0000-0003-3681-7410
authors.initials: H
authors.lastname: Choi
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
authors.forename: Taeyun
authors.initials: T
authors.lastname: Ku
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Peer
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.|Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.|Department of Chemical Engineering, MIT, Cambridge, MA, USA.|Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.|Broad Institute of Harvard University and MIT, Cambridge, MA, USA.
authors.forename: Kwanghun
authors.initials: K
authors.lastname: Chung
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria juergen.knoblich@imba.oeaw.ac.at.
authors.forename: Juergen A
authors.identifier: 0000-0002-6751-3404
authors.initials: JA
authors.lastname: Knoblich
mesh_terms: D019521:Body Patterning; D001921:Brain / Q000196:embryology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D009940:Organoids / Q000254:growth & development*; D062211:Spatio-Temporal Analysis
keywords: development; human brain development; neurogenesis; organoid; patterning; signaling