IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v501y2013i7467d10.1038_nature12517.html
   My bibliography  Save this article

Cerebral organoids model human brain development and microcephaly

Author

Listed:
  • Madeline A. Lancaster

    (Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, Austria)

  • Magdalena Renner

    (Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, Austria)

  • Carol-Anne Martin

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK)

  • Daniel Wenzel

    (Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, Austria)

  • Louise S. Bicknell

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK)

  • Matthew E. Hurles

    (Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK)

  • Tessa Homfray

    (St. George’s University, London SW17 0RE, UK)

  • Josef M. Penninger

    (Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, Austria)

  • Andrew P. Jackson

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK)

  • Juergen A. Knoblich

    (Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, Austria)

Abstract

The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

Suggested Citation

  • Madeline A. Lancaster & Magdalena Renner & Carol-Anne Martin & Daniel Wenzel & Louise S. Bicknell & Matthew E. Hurles & Tessa Homfray & Josef M. Penninger & Andrew P. Jackson & Juergen A. Knoblich, 2013. "Cerebral organoids model human brain development and microcephaly," Nature, Nature, vol. 501(7467), pages 373-379, September.
    • Handle: RePEc:nat:nature:v:501:y:2013:i:7467:d:10.1038_nature12517
    DOI: 10.1038/nature12517
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature12517
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature12517?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:501:y:2013:i:7467:d:10.1038_nature12517. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.