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

Publication ,  Journal Article
Pollen, AA; Bhaduri, A; Andrews, MG; Nowakowski, TJ; Meyerson, OS; Mostajo-Radji, MA; Di Lullo, E; Alvarado, B; Bedolli, M; Dougherty, ML ...
Published in: Cell
February 7, 2019

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.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 7, 2019

Volume

176

Issue

4

Start / End Page

743 / 756.e17

Location

United States

Related Subject Headings

  • Transcriptome
  • Species Specificity
  • Single-Cell Analysis
  • Pluripotent Stem Cells
  • Pan troglodytes
  • Organoids
  • Neurogenesis
  • Macaca
  • Induced Pluripotent Stem Cells
  • Humans
 

Citation

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Pollen, A. A., Bhaduri, A., Andrews, M. G., Nowakowski, T. J., Meyerson, O. S., Mostajo-Radji, M. A., … Kriegstein, A. R. (2019). Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution. Cell, 176(4), 743-756.e17. https://doi.org/10.1016/j.cell.2019.01.017
Pollen, Alex A., Aparna Bhaduri, Madeline G. Andrews, Tomasz J. Nowakowski, Olivia S. Meyerson, Mohammed A. Mostajo-Radji, Elizabeth Di Lullo, et al. “Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.Cell 176, no. 4 (February 7, 2019): 743-756.e17. https://doi.org/10.1016/j.cell.2019.01.017.
Pollen AA, Bhaduri A, Andrews MG, Nowakowski TJ, Meyerson OS, Mostajo-Radji MA, et al. Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution. Cell. 2019 Feb 7;176(4):743-756.e17.
Pollen, Alex A., et al. “Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.Cell, vol. 176, no. 4, Feb. 2019, pp. 743-756.e17. Pubmed, doi:10.1016/j.cell.2019.01.017.
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. Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution. Cell. 2019 Feb 7;176(4):743-756.e17.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 7, 2019

Volume

176

Issue

4

Start / End Page

743 / 756.e17

Location

United States

Related Subject Headings

  • Transcriptome
  • Species Specificity
  • Single-Cell Analysis
  • Pluripotent Stem Cells
  • Pan troglodytes
  • Organoids
  • Neurogenesis
  • Macaca
  • Induced Pluripotent Stem Cells
  • Humans