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"
}

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