title: 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.
abstract: Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.
authors.affiliation: Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Otani
authors.affiliation: Laboratory of Genetics, Salk Institute, North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Marchetto
authors.affiliation: Laboratory of Genetics, Salk Institute, North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.affiliation: Gurdon Institute, Cambridge Stem Cell Institute, and Department of Physics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address: rick@gurdon.cam.ac.uk.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Livesey
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000033:anatomy & histology* / Q000166:cytology* / Q000254:growth & development; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000166:cytology; D009929:Organ Size; D009940:Organoids / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011323:Primates / Q000033:anatomy & histology; D013045:Species Specificity