Cell stress in cortical organoids impairs molecular subtype specification. Bhaduri, A., Andrews, M. G, Mancia Leon, W., Jung, D., Shin, D., Allen, D., Jung, D., Schmunk, G., Haeussler, M., Salma, J., Pollen, A. A, Nowakowski, T. J, & Kriegstein, A. R Nature, 578(7793):142–148, January, 2020. abstract bibtex Cortical organoids are self-organizing three-dimensional cultures that model features of the developing human cerebral cortex(1,2). However, the fidelity of organoid models remains unclear(3-5). Here we analyse the transcriptomes of individual primary human cortical cells from different developmental periods and cortical areas. We find that cortical development is characterized by progenitor maturation trajectories, the emergence of diverse cell subtypes and areal specification of newborn neurons. By contrast, organoids contain broad cell classes, but do not recapitulate distinct cellular subtype identities and appropriate progenitor maturation. Although the molecular signatures of cortical areas emerge in organoid neurons, they are not spatially segregated. Organoids also ectopically activate cellular stress pathways, which impairs cell-type specification. However, organoid stress and subtype defects are alleviated by transplantation into the mouse cortex. Together, these datasets and analytical tools provide a framework for evaluating and improving the accuracy of cortical organoids as models of human brain development.
@ARTICLE{Bhaduri2020-as,
title = "Cell stress in cortical organoids impairs molecular subtype
specification",
author = "Bhaduri, Aparna and Andrews, Madeline G and Mancia Leon, Walter
and Jung, Diane and Shin, David and Allen, Denise and Jung, Dana
and Schmunk, Galina and Haeussler, Maximilian and Salma, Jahan
and Pollen, Alex A and Nowakowski, Tomasz J and Kriegstein,
Arnold R",
abstract = "Cortical organoids are self-organizing three-dimensional cultures
that model features of the developing human cerebral cortex(1,2).
However, the fidelity of organoid models remains unclear(3-5).
Here we analyse the transcriptomes of individual primary human
cortical cells from different developmental periods and cortical
areas. We find that cortical development is characterized by
progenitor maturation trajectories, the emergence of diverse cell
subtypes and areal specification of newborn neurons. By contrast,
organoids contain broad cell classes, but do not recapitulate
distinct cellular subtype identities and appropriate progenitor
maturation. Although the molecular signatures of cortical areas
emerge in organoid neurons, they are not spatially segregated.
Organoids also ectopically activate cellular stress pathways,
which impairs cell-type specification. However, organoid stress
and subtype defects are alleviated by transplantation into the
mouse cortex. Together, these datasets and analytical tools
provide a framework for evaluating and improving the accuracy of
cortical organoids as models of human brain development.",
journal = "Nature",
volume = 578,
number = 7793,
pages = "142--148",
month = jan,
year = 2020,
language = "en"
}
Downloads: 0
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However, the fidelity of organoid models remains unclear(3-5). Here we analyse the transcriptomes of individual primary human cortical cells from different developmental periods and cortical areas. We find that cortical development is characterized by progenitor maturation trajectories, the emergence of diverse cell subtypes and areal specification of newborn neurons. By contrast, organoids contain broad cell classes, but do not recapitulate distinct cellular subtype identities and appropriate progenitor maturation. Although the molecular signatures of cortical areas emerge in organoid neurons, they are not spatially segregated. Organoids also ectopically activate cellular stress pathways, which impairs cell-type specification. However, organoid stress and subtype defects are alleviated by transplantation into the mouse cortex. Together, these datasets and analytical tools provide a framework for evaluating and improving the accuracy of cortical organoids as models of human brain development.","journal":"Nature","volume":"578","number":"7793","pages":"142–148","month":"January","year":"2020","language":"en","bibtex":"@ARTICLE{Bhaduri2020-as,\n title = \"Cell stress in cortical organoids impairs molecular subtype\n specification\",\n author = \"Bhaduri, Aparna and Andrews, Madeline G and Mancia Leon, Walter\n and Jung, Diane and Shin, David and Allen, Denise and Jung, Dana\n and Schmunk, Galina and Haeussler, Maximilian and Salma, Jahan\n and Pollen, Alex A and Nowakowski, Tomasz J and Kriegstein,\n Arnold R\",\n abstract = \"Cortical organoids are self-organizing three-dimensional cultures\n that model features of the developing human cerebral cortex(1,2).\n However, the fidelity of organoid models remains unclear(3-5).\n Here we analyse the transcriptomes of individual primary human\n cortical cells from different developmental periods and cortical\n areas. We find that cortical development is characterized by\n progenitor maturation trajectories, the emergence of diverse cell\n subtypes and areal specification of newborn neurons. By contrast,\n organoids contain broad cell classes, but do not recapitulate\n distinct cellular subtype identities and appropriate progenitor\n maturation. Although the molecular signatures of cortical areas\n emerge in organoid neurons, they are not spatially segregated.\n Organoids also ectopically activate cellular stress pathways,\n which impairs cell-type specification. However, organoid stress\n and subtype defects are alleviated by transplantation into the\n mouse cortex. Together, these datasets and analytical tools\n provide a framework for evaluating and improving the accuracy of\n cortical organoids as models of human brain development.\",\n journal = \"Nature\",\n volume = 578,\n number = 7793,\n pages = \"142--148\",\n month = jan,\n year = 2020,\n language = \"en\"\n}\n\n","author_short":["Bhaduri, A.","Andrews, M. G","Mancia Leon, W.","Jung, D.","Shin, D.","Allen, D.","Jung, D.","Schmunk, G.","Haeussler, M.","Salma, J.","Pollen, A. A","Nowakowski, T. J","Kriegstein, A. 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