Article

Cerebral organoids model human brain development and microcephaly

Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, Austria.
Nature (Impact Factor: 42.35). 08/2013; 501(7467). DOI: 10.1038/nature12517
Source: PubMed

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.

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    • "Recently, a technique which allows more complex structures, i.e. " organoids " , to be produced in vitro as models of the brain per se, including various types of neurons, has been described (Lancaster et al., 2013). This technique allows multiple types of neurons to form; however, since brain regionalization in these organoids is inconsistent, there are difficul- 0922-6028/15/$35.00 "
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    • "(C) Generation of human cerebral organoids from hESCs and iPSCs. Adapted with permission from Ref. [102]. Copyright 2013, Nature Publishing Group. "
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