Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.

Journal Article (Journal Article)

Direct comparisons of human and non-human primate brains can reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. Despite metabolic differences, organoid models preserve gene regulatory networks related to primary cell types and developmental processes. We further identified 261 differentially expressed genes in human compared to both chimpanzee organoids and macaque cortex, enriched for recent gene duplications, and including multiple regulators of PI3K-AKT-mTOR signaling. We observed increased activation of this pathway in human radial glia, dependent on two receptors upregulated specifically in human: INSR and ITGB8. Our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.

Full Text

Duke Authors

Cited Authors

  • Pollen, AA; Bhaduri, A; Andrews, MG; Nowakowski, TJ; Meyerson, OS; Mostajo-Radji, MA; Di Lullo, E; Alvarado, B; Bedolli, M; Dougherty, ML; Fiddes, IT; Kronenberg, ZN; Shuga, J; Leyrat, AA; West, JA; Bershteyn, M; Lowe, CB; Pavlovic, BJ; Salama, SR; Haussler, D; Eichler, EE; Kriegstein, AR

Published Date

  • February 7, 2019

Published In

Volume / Issue

  • 176 / 4

Start / End Page

  • 743 - 756.e17

PubMed ID

  • 30735633

Pubmed Central ID

  • PMC6544371

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2019.01.017


  • eng

Conference Location

  • United States