Cerebral organoids model human brain development and microcephaly
Madeline A. Lancaster,Magdalena Renner,Carol Anne Martin,Daniel Wenzel,Louise S. Bicknell,Matthew E. Hurles,Tessa Homfray,Josef M. Penninger,Andrew P. Jackson,Juergen A. Knoblich +9 more
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TLDR
A human pluripotent stem cell-derived three-dimensional organoid culture system that develops various discrete, although interdependent, brain regions that include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes is developed.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 tissueread more
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Generation of a Motor Nerve Organoid with Human Stem Cell-Derived Neurons
Jiro Kawada,Shohei Kaneda,Takaaki Kirihara,Asif M. Maroof,Timothée Levi,Kevin Eggan,Kevin Eggan,Teruo Fujii,Yoshiho Ikeuchi +8 more
TL;DR: Generation of a nerve organoid composed of a robust fascicle of axons extended from a spheroid of human stem cell-derived motor neurons within a custom-designed microdevice should facilitate future studies on the development of the axonal fascicle and drug screening for diseases affecting axon fascicles.
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CRISPR-based functional genomics for neurological disease.
TL;DR: Perturbation of large numbers of genes in CRISPR-based genetic screens facilitates the identification of genes that are relevant for specific cellular functions.
Journal ArticleDOI
Concise Review: Drug Discovery in the Age of the Induced Pluripotent Stem Cell
Huaising C. Ko,Bruce D. Gelb +1 more
TL;DR: The incorporation of iPSC technology into drug therapy development holds promise as a more powerful and nuanced approach to personalized medicine.
Journal ArticleDOI
Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors
Reuven Edri,Yakey Yaffe,Michael J. Ziller,Naresh Mutukula,Rotem Volkman,Eyal David,Jasmine Jacob-Hirsch,Hagar Malcov,Carmit Levy,Gideon Rechavi,Irit Gat-Viks,Alexander Meissner,Yechiel Elkabetz +12 more
TL;DR: P prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state to provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modelling development in health and disease.
Journal ArticleDOI
Rbm8a Haploinsufficiency Disrupts Embryonic Cortical Development Resulting in Microcephaly
Hanqian Mao,Louis-Jan Pilaz,John J. McMahon,Christelle Golzio,Danwei Wu,Lei Shi,Nicholas Katsanis,Debra L. Silver +7 more
TL;DR: It is shown that haploinsufficiency for Rbm8a, an exon junction complex (EJC) component within 1q 21.1, causes severe microcephaly and defective neurogenesis in the mouse and indicates that disruption of RBM8A may contribute to neurodevelopmental phenotypes associated with proximal 1q21.1 microdeletions.
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