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: 41.46). 08/2013; 501(7467). DOI: 10.1038/nature12517
Source: PubMed


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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Available from: Madeline Lancaster, Sep 09, 2014
    • "Moreover, from human iPSCs, Lancaster and colleagues were able to generate cerebral organoids, a three dimensional structure that contains areas which resemble specific independent brain regions such as cerebral cortex ([36] and Fig. 1)). Using this model, neuronal differentiation analysis from patients with microcephaly could be performed [36]. The facts that these regions contain neuronal progenitors which can reach a mature state allow the opportunity for example to study cell–cell interactions, time course of cell differentiation in both normal and pathological conditions. "
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    ABSTRACT: Adult cells from patients can be reprogrammed to induced pluripotent stem cells (iPSCs) which successively can be used to obtain specific cells such as neurons. This remarkable breakthrough represents a new way of studying diseases and brought new therapeutic perspectives in the field of Regenerative Medicine. This is particular true in the neurology field, where few techniques are amenable to study the affected tissue of the patient during disease progression and many diseases are lacking neuroprotective therapies or any therapy at all. In this review we discuss the advantages and unresolved issues of cell reprogramming and neuronal differentiation. We reviewed evidence using iPSCs-derived neurons from neurological patients. Focusing on data obtained from Parkinson's disease (PD) patients, we show that iPSC-derived neurons possess morphological and functional characteristics of this disease and build a case for the use of this technology to study PD and other neuropathologies while disease is in progress. These data show the enormous impact that this new technology starts to have on different purposes such as the study and design of future therapies of neurological disease, especially PD. Copyright © 2015. Published by Elsevier B.V.
    FEBS letters 07/2015; 589(22). DOI:10.1016/j.febslet.2015.07.023 · 3.17 Impact Factor
    • "The region in the white box identifies an area with appropriate apical/basal organization of NPCs and neurons surrounding a ventriclelike structure (Lancaster and others 2013). Bottom images show the development of organoids from iPSCs to fully formed structures (Lancaster and others 2013). (C) Labeling of endogenous proteins in living cells will allow the dynamic study of synaptic components without affecting the function of the synapse. "
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    The Neuroscientist 07/2015; DOI:10.1177/1073858415596131 · 6.84 Impact Factor
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    • "Lancaster et al. (2013) reported the development of brain tissue from hiPSCs, termed cerebral organoids. Cerebral organoids consisted of discrete regions similar to the cerebral cortex, ventricles and retina tissue , and recapitulated some key aspects of human cortical development mentioned above (Lancaster et al., 2013). Similarly, Meyer et al. (2011) showed that hiPSCs can be differentiated into 3D retinal structures consisting of multiple retinal cell types, in a time frame similar to normal human retinal development (Meyer et al., 2011). "
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