Journal
NATURE
Volume 501, Issue 7467, Pages 373-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12517
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Funding
- Wellcome Trust [WT098051]
- Austrian Academy of Sciences
- Austrian Science Fund (FWF) [Z153-B09, I552-B19]
- ERC
- EMBO
- Helen Hay Whitney
- Medical Research Council
- European Research Council (ERC)
- Lister Institute for Preventative Medicine
- Austrian Science Fund (FWF) [Z153] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [Z 153] Funding Source: researchfish
- Medical Research Council [MC_PC_U127580972] Funding Source: researchfish
- MRC [MC_PC_U127580972] Funding Source: UKRI
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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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