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Cerebral organoids model human brain development and microcephaly

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    Rights statement: Published in final edited form as: Nature. Sep 19, 2013; 501(7467): 10.1038/nature12517. Published online Aug 28, 2013. doi: 10.1038/nature12517

    Accepted author manuscript, 3.67 MB, PDF document

http://www.nature.com/nature/journal/v501/n7467/full/nature12517.html
Original languageEnglish
Pages (from-to)373-9
Number of pages7
JournalNature
Volume501
Issue number7467
DOIs
Publication statusPublished - 19 Sep 2013

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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