Publication Date:
2013-09-03
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817409/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817409/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lancaster, Madeline A -- Renner, Magdalena -- Martin, Carol-Anne -- Wenzel, Daniel -- Bicknell, Louise S -- Hurles, Matthew E -- Homfray, Tessa -- Penninger, Josef M -- Jackson, Andrew P -- Knoblich, Juergen A -- 250342/European Research Council/International -- I 552/Austrian Science Fund FWF/Austria -- MC_PC_U127580972/Medical Research Council/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Z 153/Austrian Science Fund FWF/Austria -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Sep 19;501(7467):373-9. doi: 10.1038/nature12517. Epub 2013 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna 1030, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23995685" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Brain/anatomy & histology/cytology/*growth & development/*pathology
;
Cerebral Cortex/cytology/embryology/growth & development/pathology
;
Humans
;
Induced Pluripotent Stem Cells/cytology/pathology
;
Mice
;
Microcephaly/*pathology
;
*Models, Biological
;
Neural Stem Cells/cytology/pathology
;
Neurogenesis
;
Neurons/cytology/pathology
;
Organoids/*cytology/embryology/*growth & development/pathology
;
Tissue Culture Techniques/*methods
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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