Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution. Pollen, A. A, Bhaduri, A., Andrews, M. G, Nowakowski, T. J, Meyerson, O. S, Mostajo-Radji, M. A, Di Lullo, E., Alvarado, B., Bedolli, M., Dougherty, M. L, Fiddes, I. T, Kronenberg, Z. N, Shuga, J., Leyrat, A. A, West, J. A, Bershteyn, M., Lowe, C. B, Pavlovic, B. J, Salama, S. R, Haussler, D., Eichler, E. E, & Kriegstein, A. R Cell, 176(4):743–756.e17, February, 2019. abstract bibtex 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.
@ARTICLE{Pollen2019-vm,
title = "Establishing Cerebral Organoids as Models of {Human-Specific}
Brain Evolution",
author = "Pollen, Alex A and Bhaduri, Aparna and Andrews, Madeline G and
Nowakowski, Tomasz J and Meyerson, Olivia S and Mostajo-Radji,
Mohammed A and Di Lullo, Elizabeth and Alvarado, Beatriz and
Bedolli, Melanie and Dougherty, Max L and Fiddes, Ian T and
Kronenberg, Zev N and Shuga, Joe and Leyrat, Anne A and West, Jay
A and Bershteyn, Marina and Lowe, Craig B and Pavlovic, Bryan J
and Salama, Sofie R and Haussler, David and Eichler, Evan E and
Kriegstein, Arnold R",
abstract = "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.",
journal = "Cell",
volume = 176,
number = 4,
pages = "743--756.e17",
month = feb,
year = 2019,
keywords = "cerebral organoids; chimpanzee; cortical development;
human-specific evolution; mTOR; macaque; neural progenitor cells;
radial glia; single-cell RNA sequencing",
language = "en"
}
Downloads: 0
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Our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.","journal":"Cell","volume":"176","number":"4","pages":"743–756.e17","month":"February","year":"2019","keywords":"cerebral organoids; chimpanzee; cortical development; human-specific evolution; mTOR; macaque; neural progenitor cells; radial glia; single-cell RNA sequencing","language":"en","bibtex":"@ARTICLE{Pollen2019-vm,\n title = \"Establishing Cerebral Organoids as Models of {Human-Specific}\n Brain Evolution\",\n author = \"Pollen, Alex A and Bhaduri, Aparna and Andrews, Madeline G and\n Nowakowski, Tomasz J and Meyerson, Olivia S and Mostajo-Radji,\n Mohammed A and Di Lullo, Elizabeth and Alvarado, Beatriz and\n Bedolli, Melanie and Dougherty, Max L and Fiddes, Ian T and\n Kronenberg, Zev N and Shuga, Joe and Leyrat, Anne A and West, Jay\n A and Bershteyn, Marina and Lowe, Craig B and Pavlovic, Bryan J\n and Salama, Sofie R and Haussler, David and Eichler, Evan E and\n Kriegstein, Arnold R\",\n abstract = \"Direct comparisons of human and non-human primate brains can\n reveal molecular pathways underlying remarkable specializations\n of the human brain. However, chimpanzee tissue is inaccessible\n during neocortical neurogenesis when differences in brain size\n first appear. To identify human-specific features of cortical\n development, we leveraged recent innovations that permit\n generating pluripotent stem cell-derived cerebral organoids from\n chimpanzee. Despite metabolic differences, organoid models\n preserve gene regulatory networks related to primary cell types\n and developmental processes. We further identified 261\n differentially expressed genes in human compared to both\n chimpanzee organoids and macaque cortex, enriched for recent gene\n duplications, and including multiple regulators of PI3K-AKT-mTOR\n signaling. We observed increased activation of this pathway in\n human radial glia, dependent on two receptors upregulated\n specifically in human: INSR and ITGB8. 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