Cerebral organoids model human brain development and microcephaly View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-09

AUTHORS

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

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. More... »

PAGES

373

References to SciGraph publications

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  • Journal

    TITLE

    Nature

    ISSUE

    7467

    VOLUME

    501

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature12517

    DOI

    http://dx.doi.org/10.1038/nature12517

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1019617574

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23995685


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